FEBS Letters RSS feed: Current Issue. FEBS Letters is one of the world's leading journals in biochemistry and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, hypotheses and research letters that merit urgent publication. FEBS Letters offers: • Faster publication: ? Accepted articles are published online in 3 days ? The print version of the article is published in 3 to 5 weeks after acceptance • Full-text article disclosure in HTML and PDF formats • Articles in Press are included in PubMed • Easy online manuscript submission system • Transparent online peer review and manuscript tracking system • No page charges • Free color figures Subject Coverage: The subject area of FEBS Letters is broad. It covers biochemistry (including protein chemistry, enzymology, nucleic acid chemistry, metabolism, and immunochemistry), structural biology, biophysics, computational biology (genomics, proteomics, bioinformatics), molecular genetics, molecular biology and molecular cell biology (signal transduction, intracellular traffic, regulation of cellular proliferation, cell-cell interactions) and systems biology. Studies on microbes, plants and animals at the molecular level are within the scope of FEBS Letters. Submitting Authors: Manuscripts can be submitted to FEBS Letters at: http://ees.elsevier.com/febsletters/ http://www.febsletters.org/?rss=yesElsevier Inc.en © 2010 Published by Elsevier Inc. All rights reserved. FEBS Letters0014-5793584154 August 2010 © 2010 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.febsletters.org/article/PIIS0014579310005454/abstract?rss=yesEditorial Board10.1016/S0014-5793(10)00545-4FEBS Letters 584, 15 (2010)2010-08-04FEBS Letters2010-08-0458415S0014-5793(10)X0014-Xiihttp://www.febsletters.org/article/PIIS0014579310005090/abstract?rss=yesPeroxisome proliferator-activated receptors (PPARs) build up a superfamily of receptors consisting of nearly 50 ligand-dependent transcription factors. Originally, PPARs were discovered by their ability to induce hepatic peroxisome proliferation in rodents in response to xenobiotic stimuli. So far three PPAR isoforms were described, α, β/δ and γ, that are encoded by different genes and are differentially expressed in various organs.Focus on…the role of PPARγ in adipogenesisWilhelm Just10.1016/j.febslet.2010.06.018FEBS Letters 584, 15 (2010)2010-06-18FEBS Letters2010-06-1858415S0014-5793(10)X0014-XIntroduction32413241http://www.febsletters.org/article/PIIS0014579310004928/abstract?rss=yesAbstract: Adipocyte differentiation is controlled by a tightly regulated transcriptional cascade in which PPARγ and members of the C/EBP family are key players. Here we review the roles of PPARγ and C/EBPs in adipocyte differentiation with emphasis on the recently published genome-wide binding profiles for PPARγ and C/EBPα. Interestingly, these analyses show that PPARγ and C/EBPα binding sites are associated with most genes that are induced during adipogenesis suggesting direct activation of many more adipocyte genes than previously anticipated. Furthermore, an extensive overlap between the C/EBPα and PPARγ cistromes indicate a hitherto unrecognized direct crosstalk between these transcription factors. As more genome-wide data emerge in the future, this crosstalk will likely be found to include several other adipogenic transcription factors.PPARγ in adipocyte differentiation and metabolism – Novel insights from genome-wide studiesRasmus Siersbæk, Ronni Nielsen, Susanne Mandrup10.1016/j.febslet.2010.06.010FEBS Letters 584, 15 (2010)2010-06-11FEBS Letters2010-06-1158415S0014-5793(10)X0014-XReviews32423249http://www.febsletters.org/article/PIIS0014579310005302/abstract?rss=yesAbstract: The development of adipose tissue is a process which involves the concerted cooperation of numerous transcription factors together with their coactivators and corepressors. The peroxisome proliferator-activated receptor γ (PPARγ) is considered to be one of the master regulators of adipocyte differentiation. The presence of two functionally distinct types of adipose tissue, white and brown (WAT and BAT), requires an even more complex regulation of adipose tissue development. In this review we will focus on the role of PPARγ coregulators in adipogenesis and especially on the role of PPARγ coregulators in white and brown adipose tissue. Specificity in coregulator function in WAT and BAT may form an additional level of regulation of adipose tissue development.Brown vs white adipocytes: The PPARγ coregulator storyArjen Koppen, Eric Kalkhoven10.1016/j.febslet.2010.06.035FEBS Letters 584, 15 (2010)2010-06-29FEBS Letters2010-06-2958415S0014-5793(10)X0014-XReviews32503259http://www.febsletters.org/article/PIIS0014579310004230/abstract?rss=yesAbstract: Transcriptional co-activators, co-repressors and chromatin remodeling machines are essential elements in the transcriptional programs directed by the master adipogenic transcription factor PPARγ. Many of these components have orthologs in other organisms, where they play roles in development and pattern formation, suggesting new links between cell fate decision-making and adipogenesis. This review focuses on bromodomain-containing protein complexes recently shown to play a critical role in adipogenesis. Deeper understanding of these pathways is likely to have major impact on treatment of obesity-associated diseases, including metabolic syndrome, cardiovascular disease and Type 2 diabetes. The research effort is urgent because the obesity epidemic is serious; the medical community is ill prepared to cope with the anticipated excess morbidity and mortality associated with diet-induced obesity.An emerging role for bromodomain-containing proteins in chromatin regulation and transcriptional control of adipogenesisGerald V. Denis, Barbara S. Nikolajczyk, Gavin R. Schnitzler10.1016/j.febslet.2010.05.030FEBS Letters 584, 15 (2010)2010-05-20FEBS Letters2010-05-2058415S0014-5793(10)X0014-XReviews32603268http://www.febsletters.org/article/PIIS0014579310005193/abstract?rss=yesAbstract: S100 proteins interact with the transactivation domain and the C-terminus of p53. Further, S100B has been shown to interact with MDM2, a central negative regulator of p53. Here, we show that S100B bound directly to the folded N-terminal domain of MDM2 (residues 2-125) by size exclusion chromatography and surface plasmon resonance experiments. This interaction with MDM2 (2-125) is a general feature of S100 proteins; S100A1, S100A2, S100A4 and S100A6 also interact with MDM2 (2-125). These interactions with S100 proteins do not result in a ternary complex with MDM2 (2-125) and p53. Instead, we observe the ability of a subset of S100 proteins to disrupt the extent of MDM2-mediated p53 ubiquitylation in vitro.Structured summary: MINT-7905256: MDM2 (uniprotkb:Q00987) binds (MI:0407) to s100A6 (uniprotkb:P06703) by surface plasmon resonance (MI:0107)MINT-7905063: MDM2 (uniprotkb:Q00987) and s100A1 (uniprotkb:P23297) bind (MI:0407) by molecular sieving (MI:0071)MINT-7905376: s100A4 (uniprotkb:P26447) and MDM2 (uniprotkb:Q00987) physically interact (MI:0915) by competition binding (MI:0405)MINT-7905130: s100A6 (uniprotkb:P06703) and MDM2 (uniprotkb:Q00987) bind (MI:0407) by molecular sieving (MI:0071)MINT-7905207: s100A6 (uniprotkb:P06703) and p53 (uniprotkb:P04637) bind (MI:0407) by molecular sieving (MI:0071)MINT-7905043: s100B (uniprotkb:P04271) and MDM2 (uniprotkb:Q00987) bind (MI:0407) by molecular sieving (MI:0071)MINT-7905196: p53 (uniprotkb:P04637) and s100A4 (uniprotkb:P26447) bind (MI:0407) by molecular sieving (MI:0071)MINT-7905358: p53 (uniprotkb:P04637) and s100A4 (uniprotkb:P26447) physically interact (MI:0915) by fluorescence polarization spectroscopy (MI:0053)MINT-7905220: MDM2 (uniprotkb:Q00987) binds (MI:0407) to s100B (uniprotkb:P04271) by surface plasmon resonance (MI:0107)MINT-7905104: s100A4 (uniprotkb:P26447) and MDM2 (uniprotkb:Q00987) bind (MI:0407) by molecular sieving (MI:0071)MINT-7905229: MDM2 (uniprotkb:Q00987) binds (MI:0407) to s100A1 (uniprotkb:P23297) by surface plasmon resonance (MI:0107)MINT-7905317, MINT-7905162: s100B (uniprotkb:P04271) and p53 (uniprotkb:P04637) bind (MI:0407) by molecular sieving (MI:0071)MINT-7905238: MDM2 (uniprotkb:Q00987) binds (MI:0407) to s100A2 (uniprotkb:P29034) by surface plasmon resonance (MI:0107)MINT-7905174, MINT-7905308: s100A1 (uniprotkb:P23297) and p53 (uniprotkb:P04637) bind (MI:0407) by molecular sieving (MI:0071)MINT-7905247: MDM2 (uniprotkb:Q00987) binds (MI:0407) to s100A4 (uniprotkb:P26447) by surface plasmon resonance (MI:0107)MINT-7905090: s100A2 (uniprotkb:P29034) and MDM2 (uniprotkb:Q00987) bind (MI:0407) by molecular sieving (MI:0071)MINT-7905142, MINT-7905326: MDM2 (uniprotkb:Q00987) and p53 (uniprotkb:P04637) bind (MI:0407) by molecular sieving (MI:0071)MINT-7905185, MINT-7905347: s100A2 (uniprotkb:P29034) and p53 (uniprotkb:P04637) bind (MI:0407) by molecular sieving (MI:0071)S100 proteins interact with the N-terminal domain of MDM2Jan van Dieck, Jenifer K. Lum, Daniel P. Teufel, Alan R. Fersht10.1016/j.febslet.2010.06.024FEBS Letters 584, 15 (2010)2010-06-21FEBS Letters2010-06-2158415S0014-5793(10)X0014-XResearch Letters with SDA32693274http://www.febsletters.org/article/PIIS0014579310005223/abstract?rss=yesAbstract: The SCY1-like 1 binding protein 1 (SCYL1-BP1) protein was identified as an interacting partner of E3 ligase p53-induced RING H2 protein (Pirh2) and mouse double minute gene number 2 (MDM2) by yeast two-hybrid screening. Further investigation suggested there are two interactions involved in different mechanisms. SCYL1-BP1 can be ubiquitinated and degraded by Pirh2 but not by MDM2, which suggests that SCYL1-BP1 can be regulated by Pirh2. On the other hand, while SCYL1-BP1 binds to ubiquitin E3 ligase MDM2, it promotes MDM2 self-ubiquitination and results in a reduction of MDM2 protein level.Structured summary: MINT-7904819, MINT-7904837, MINT-7904806, MINT-7904715: MDM2 (uniprotkb:Q00987) physically interacts (MI:0915) with SCYL1-BP1 (uniprotkb:Q5T7V8) by anti tag coimmunoprecipitation (MI:0007)MINT-7904857, MINT-7904899: SCYL1-BP1 (uniprotkb:Q5T7V8) physically interacts (MI:0915) with MDM2 (uniprotkb:Q00987) by anti bait coimmunoprecipitation (MI:0006)A newly identified Pirh2 substrate SCYL1-BP1 can bind to MDM2 and accelerate MDM2 self-ubiquitinationJing Yan, Di Zhang, Yujun Di, Huili Shi, Hai Rao, Keke Huo10.1016/j.febslet.2010.06.027FEBS Letters 584, 15 (2010)2010-06-23FEBS Letters2010-06-2358415S0014-5793(10)X0014-XResearch Letters with SDA32753278http://www.febsletters.org/article/PIIS0014579310005247/abstract?rss=yesAbstract: Macropinocytosis is regulated by Abl kinase via an unknown mechanism.We previously demonstrated that Abl kinase activity is, itself, regulated by Abi1 subsequent to Abl kinase phosphorylation of Abi1 tyrosine 213 (pY213) .Here we show that blocking phosphorylation of Y213 abrogated the ability of Abl to regulate macropinocytosis, implicating Abi1 pY213 as a key regulator of macropinocytosis.Results from screening the human SH2 domain library and mapping the interaction site between Abi1 and the p85 regulatory domain of PI-3 kinase, coupled with data from cells transfected with loss-of-function p85 mutants, support the hypothesis that macropinocytosis is regulated by interactions between Abi1 pY213 and the C-terminal SH2 domain of p85—thereby linking Abl kinase signaling to p85-dependent regulation of macropinocytosis.Structured summary: MINT-7908602:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to SHIP2 (uniprotkb:O15357) by array technology (MI:0008)MINT-7908362:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Emt (uniprotkb:Q08881) by array technology (MI:0008)MINT-7908235:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Lyn (uniprotkb:P07948) by array technology (MI:0008)MINT-7908075:Abi1 (uniprotkb:Q8IZP0)binds(MI:0407) to Fgr (uniprotkb:P09769) by array technology (MI:0008)MINT-7908330, MINT-7908522:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Vav1 (uniprotkb:P15498) by array technology (MI:0008)MINT-7907962:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Fyn (uniprotkb:P06241) by array technology (MI:0008)MINT-7908203:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Src(uniprotkb:P12931) by array technology (MI:0008)MINT-7908570:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to SHP-2 (uniprotkb:P35235) by array technology (MI:0008)MINT-7908187, MINT-7908586:Abi1(uniprotkb:Q8IZP0) binds (MI:0407) to Gap (uniprotkb:P20936) by array technology (MI:0008)MINT-7907981, MINT-7907995:Abi1 (uniprotkb:Q8IZP0) physically interacts (MI:0915) with p85a(uniprotkb:P26450) by anti tag coimmunoprecipitation (MI:0007)MINT-7908251:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to PLCG1 (uniprotkb:P19174) by array technology (MI:0008)MINT-7908346:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Grb2 (uniprotkb:P62993) by array technology (MI:0008)MINT-7907945:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Abl (uniprotkb:P00519) by array technology (MI:0008)MINT-7908474:Abi1(uniprotkb:Q8IZP0)binds (MI:0407) to p85b (uniprotkb:O00459) by array technology (MI:0008)MINT-7908107:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Hck (uniprotkb:P08631) by array technology (MI:0008)MINT-7908011: p85a (uniprotkb:P26450) physically interacts (MI:0915) with Abi1 (uniprotkb:Q8IZP0) by pull down (MI:0096)MINT-7908155:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to FynT (uniprotkb:P06241-2) by array technology (MI:0008)MINT-7908283, MINT-7908490:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to p55g (uniprotkb:Q92569) by array technology (MI:0008)MINT-7907929, MINT-7907815, MINT-7907832, MINT-7907865, MINT-7907897, MINT-7907913, MINT-7907881, MINT-7907848:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to p85a (uniprotkb:P27986) by array technology (MI:0008)MINT-7908059:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Frk (uniprotkb:P42685) by array technology (MI:0008)MINT-7908378:Abi1(uniprotkb:Q8IZP0) binds (MI:0407) to CblC (uniprotkb:Q9ULV8) by array technology (MI:0008)MINT-7908618:Abi1(uniprotkb:Q8IZP0) binds (MI:0407) to CblA (uniprotkb:B5MC15) by array technology (MI:0008)MINT-7908139, MINT-7908538:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Nap4 (uniprotkb:O14512) by array technology (MI:0008)MINT-7908426:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to CblB (uniprotkb:Q13191) by array technology (MI:0008)MINT-7908506:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Crk (uniprotkb:P46108) by array technology (MI:0008)MINT-7908554:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to mAbl (uniprotkb:P00520) by array technology (MI:0008)MINT-7908043, MINT-7908394:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Vav2 (uniprotkb:P52735) by array technology (MI:0008)MINT-7908458:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to mSck/ShcB (uniprotkb:Q8BMC3) by array technology (MI:0008)MINT-7908091:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Yes (uniprotkb:P07947) by array technology (MI:0008)MINT-7908219:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Src (uniprotkb:P00523) by array technology (MI:0008)MINT-7908123:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Fer (uniprotkb:P16591) by array technology (MI:0008)MINT-7908410:Abi1(uniprotkb:Q8IZP0) binds (MI:0407) to CrkL (uniprotkb:P46109) by array technology (MI:0008)MINT-7908314, MINT-7908442:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Arg (uniprotkb:P42684) by array technology (MI:0008)MINT-7908299:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to PLCG1 (uniprotkb:P10686) by array technology (MI:0008)MINT-7908171:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Fes (uniprotkb:P07332) by array technology (MI:0008)MINT-7908027:Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Lck (uniprotkb:P06239) by array technology (MI:0008)Abi1/Hssh3bp1 pY213 links Abl kinase signaling to p85 regulatory subunit of PI-3 kinase in regulation of macropinocytosis in LNCaP cellsPatrycja M. Dubielecka, Kazuya Machida, Xiaoling Xiong, Sajjad Hossain, Mari Ogiue-Ikeda, Ana C. Carrera, Bruce J. Mayer, Leszek Kotula10.1016/j.febslet.2010.06.029FEBS Letters 584, 15 (2010)2010-06-23FEBS Letters2010-06-2358415S0014-5793(10)X0014-XResearch Letters with SDA32793286http://www.febsletters.org/article/PIIS0014579310005181/abstract?rss=yesAbstract: Vitronectin is a multi-functional protein found predominantly as a monomer in blood and as an oligomer in the extracellular matrix. We have dissected the minimal regions of vitronectin protein needed for effective integrin dependent cell adhesion and spreading. A fragment of vitronectin containing the RGD integrin binding site showed similar binding affinity as that of full vitronectin protein to purified integrin αvβ3 but had diminished cell adhesion and spreading function in vivo. We demonstrate that the oligomeric state of the protein is responsible for this effect. We provide compelling evidence for the involvement of the heparin binding domain of vitronectin in the oligomerization process and show that such oligomerization reinforces the activity of vitronectin in cell adhesion and spreading.Structured summary: MINT-7905703: Vn (uniprotkb:P04004) and Vn (uniprotkb:P04004) bind (MI:0407) by molecular sieving (MI:0071)Heparin binding domain in vitronectin is required for oligomerization and thus enhances integrin mediated cell adhesion and spreadingChandramouli R Chillakuri, Céline Jones, Helen J Mardon10.1016/j.febslet.2010.06.023FEBS Letters 584, 15 (2010)2010-06-21FEBS Letters2010-06-2158415S0014-5793(10)X0014-XResearch Letters with SDA32873291http://www.febsletters.org/article/PIIS0014579310005636/abstract?rss=yesAbstract: RanGTP mediates nuclear import and mitotic spindle assembly by dissociating import receptors from nuclear localization signal (NLS) bearing proteins. We investigated the interplay between import receptors and the transmembrane nucleoporin Pom121. We found that Pom121 interacts with importin α/β and a group of nucleoporins in an NLS-dependent manner. In vivo, replacement of Pom121 with an NLS mutant version resulted in defective nuclear transport, induction of aberrant cytoplasmic membrane stacks and decreased cell viability. We propose that the NLS sites of Pom121 affect its function in NPC assembly both by influencing nucleoporin interactions and pore membrane structure.Structured summary: MINT-7951230: pom121 (uniprotkb:Q5EWX9) physically interacts (MI:0914) with nup155 (uniprotkb:O75694), Nup133 (uniprotkb:Q8WUM0) and Importin beta (uniprotkb:Q14974) by pull down (MI:0096)MINT-7951210: pom121 (uniprotkb:Q5EWX9) physically interacts (MI:0915) with Importin alpha (uniprotkb:P52170) and Importin beta (uniprotkb:P52297) by pull down (MI:0096)MINT-7951183: pom121 (uniprotkb:Q5EWX9) physically interacts (MI:0914) with nup155 (uniprotkb:Q7ZWL0), nup160 (uniprotkb:P83722), nup205 (uniprotkb:Q642R6), nup93 (uniprotkb:Q7ZX96), Importin beta (uniprotkb:P52297) and nup62 (uniprotkb:Q91349) by pull down (MI:0096)MINT-7951416: pom121 (uniprotkb:Q5EWX9) physically interacts (MI:0914) with nup155 (uniprotkb:Q7ZWL0), nup93 (uniprotkb:Q7ZX96) and Importin beta (uniprotkb:P52297) by pull down (MI:0096)MINT-7951276: pom121 (uniprotkb:Q5EWX9) physically interacts (MI:0914) with nup155 (uniprotkb:Q7ZWL0), nup205 (uniprotkb:Q642R6), nup93 (uniprotkb:Q7ZX96), Importin beta (uniprotkb:P52297) and nup62 (uniprotkb:Q91349) by pull down (MI:0096)MINT-7951306, MINT-7951362: pom121 (uniprotkb:Q5EWX9) physically interacts (MI:0914) with nup155 (uniprotkb:Q7ZWL0), nup160 (uniprotkb:P83722), nup93 (uniprotkb:Q7ZX96), Importin beta (uniprotkb:P52297) and nup62 (uniprotkb:Q91349) by pull down (MI:0096)NLS-mediated NPC functions of the nucleoporin Pom121Sevil Yavuz, Rachel Santarella-Mellwig, Birgit Koch, Andreas Jaedicke, Iain W. Mattaj, Wolfram Antonin10.1016/j.febslet.2010.07.008FEBS Letters 584, 15 (2010)2010-07-12FEBS Letters2010-07-1258415S0014-5793(10)X0014-XResearch Letters with SDA32923298http://www.febsletters.org/article/PIIS0014579310005557/abstract?rss=yesAbstract: The 5′ cap trimethylation of small nuclear (snRNAs) and several nucleolar RNAs (snoRNAs) by trimethylguanosine synthase 1 (Tgs1p) is required for efficient pre-mRNA splicing. The previously uncharacterised protein Swm2p interacted with Tgs1p in yeast two-hybrid screens. In the present study we show that Swm2p interacts with the N-terminus of Tgs1p and its deletion impairs pre-mRNA splicing and pre-rRNA processing. The trimethylation of spliceosomal snRNAs and the U3 snoRNA, but not other snoRNAs, was abolished in the absence of Swm2p, indicating that Swm2p is required for a substrate-specific activity of Tgs1p.Structured summary: MINT-7949608: p53 (uniprotkb:P02340) physically interacts (MI:0915) with large T-antigen (uniprotkb:P03070) by two-hybrid (MI:0018)MINT-7949574: swm2 (uniprotkb:P40342) physically interacts (MI:0915) with swm2 (uniprotkb:P40342) by pull down (MI:0096)MINT-7949556: swm2 (uniprotkb:P40342) physically interacts (MI:0915) with TGS1 (uniprotkb:Q12052) by pull down (MI:0096)MINT-7949587: swm2 (uniprotkb:P40342) physically interacts (MI:0915) with tgs1 (uniprotkb:Q12052) by two-hybrid (MI:0018)MINT-7949641: nop1 (uniprotkb:P15646) colocalizes (MI:0403) with TGS1 (uniprotkb:Q12052) by fluorescence microscopy (MI:0416)MINT-7949627: swm2 (uniprotkb:P40342) and nop1 (uniprotkb:P15646) colocalize (MI:0403) by fluorescence microscopy (MI:0416)MINT-7949540: swm2 (uniprotkb:P40342) physically interacts (MI:0915) with TGS1 (uniprotkb:Q12052) by tandem affinity purification (MI:0676)Deletion of Swm2p selectively impairs trimethylation of snRNAs by trimethylguanosine synthase (Tgs1p)Kum-Loong Boon, Martin Koš10.1016/j.febslet.2010.07.001FEBS Letters 584, 15 (2010)2010-07-09FEBS Letters2010-07-0958415S0014-5793(10)X0014-XResearch Letters with SDA32993304http://www.febsletters.org/article/PIIS0014579310005569/abstract?rss=yesAbstract: Protein–protein interactions between the Bcl2 family proteins regulate apoptosis. An imbalance of this interaction network due to the upregulation of the proto-oncogene Bcl2 leads to a resistance to apoptosis associated with tumor formation. Bcl2 overexpression inhibits BAX oligomerization and mitochondrial outer membrane (MOM) permeabilization. However, Bcl2 effects on earlier steps of BAX-mediated apoptosis are not fully understood. Bcl2 overexpression inhibits BAX insertion into the MOM but spontaneously increases BAX relocalization to the mitochondria. Also, a physical interaction between BAX and Bcl2 is necessary for these two effects to occur. Taken together, these results suggest upregulated Bcl2 stabilizes BAX loose binding to mitochondrial membranes, inhibiting its insertion into the MOM and consequently cytochrome c release.Structured summary: MINT-7945271: BAX (uniprotkb:Q07813) physically interacts (MI:0915) with Bcl-2 (uniprotkb:P10417) by anti bait coimmunoprecipitation (MI:0006)Upregulation of Bcl2 inhibits apoptosis-driven BAX insertion but favors BAX relocalization in mitochondriaO. Teijido, L. Dejean10.1016/j.febslet.2010.07.002FEBS Letters 584, 15 (2010)2010-07-09FEBS Letters2010-07-0958415S0014-5793(10)X0014-XResearch Letters with SDA33053310http://www.febsletters.org/article/PIIS0014579310005673/abstract?rss=yesAbstract: The calponin homology-associated smooth muscle protein (CHASM) can modulate muscle contractility, and its biological action may involve an interaction with the contractile filament. In this study, we demonstrate an interaction between CHASM and tropomyosin. Deletion constructs of CHASM were generated, and pull-down assays revealed a minimal deletion construct that could bind tropomyosin. Removal of the calponin homology (CH) domain or expression of the CH domain alone did not enable binding. The interaction was characterized by microcalorimetry with a dissociation constant of 2.0×10−6M. Confocal fluorescence microscopy also showed green fluorescent protein (GFP)–CHASM localization to filamentous structures within smooth muscle cells, and this targeting was dependent upon the CH domain.Structured summary: MINT-7966126: CHASM (uniprotkb:Q99LM3), Tropomyosin alpha (uniprotkb:P04268) and Tropomyosin beta (uniprotkb:P19352) physically interact (MI:0915) by isothermal titration calorimetry (MI:0065)MINT-7966073: CHASM (uniprotkb:Q99LM3) physically interacts (MI:0914) with Tropomyosin beta (uniprotkb:P58776) and Tropomyosin alpha (uniprotkb:P58772) by pull down (MI:0096)MINT-7966187: Tropomyosin alpha (uniprotkb:P04268) and Tropomyosin beta (uniprotkb:P19352) physically interact (MI:0915) with CHASM (uniprotkb:Q99LM3) by pull down (MI:0096)MINT-7966090: CHASM (uniprotkb:Q99LM3) binds (MI:0407) to Tropomyosin alpha (uniprotkb:P04268) by pull down (MI:0096)Tropomyosin-binding properties of the CHASM protein are dependent upon its calponin homology domainAnnegret Ulke-Lemée, Hiroaki Ishida, Meredith A. Borman, Alexandra Valderrama, Hans J. Vogel, Justin A. MacDonald10.1016/j.febslet.2010.07.012FEBS Letters 584, 15 (2010)2010-07-12FEBS Letters2010-07-1258415S0014-5793(10)X0014-XResearch Letters with SDA33113316http://www.febsletters.org/article/PIIS0014579310005697/abstract?rss=yesAbstract: Although CaV1.2 and CaV1.3 are two subtypes of L-type Ca2+ channels expressed in the CNS, functions of CaV1.3 have not been well elucidated compared to CaV1.2. Here, we found that CaV1.3-NT associates with GABABR2-CT using yeast two-hybrid, GST pull-down and co-immunoprecipitation assays. We also demonstrated co-localization of CaV1.3 and GABABR2 in HEK293 cells and cultured hippocampal neurons. Whole-cell patch-clamp and Ca2+-imaging experiments revealed that activation of GABABR increases CaV1.3 currents and intracellular Ca2+ via CaV1.3, but not CaV1.2. These results show a physical and functional interaction between CaV1.3 and GABABR, suggesting the potential pivotal roles of CaV1.3 in the CNS.Structured summary: MINT-7975667: Cav1.3 (uniprotkb:P27732) physically interacts (MI:0915) with GABABR2 (uniprotkb:O88871) by two hybrid (MI:0018)MINT-7975740: Cav1.3 (uniprotkb:P27732) and GABABR2 (uniprotkb:O75899) colocalize (MI:0403) by fluorescence microscopy (MI:0416)MINT-7966007, MINT-7966016: Cav1.3 (uniprotkb:P27732) physically interacts (MI:0915) with GABABR2 (uniprotkb:O88871) by anti bait coimmunoprecipitation (MI:0006)MINT-7975712, MINT-7975691: Cav1.3 (uniprotkb:P27732) physically interacts (MI:0915) with GABABR2 (uniprotkb:O88871) by pull down (MI:0096)MINT-7966026: GABABR2 (uniprotkb:O88871) and Cav1.3 (uniprotkb:P27732) colocalize (MI:0403) by fluorescence microscopy (MI:0416)Direct interaction and functional coupling between voltage-gated CaV1.3 Ca2+ channel and GABAB receptor subunit 2Hye-Won Park, Hana Jung, Kee-Hyun Choi, Ja-Hyun Baik, Hyewhon Rhim10.1016/j.febslet.2010.07.014FEBS Letters 584, 15 (2010)2010-07-12FEBS Letters2010-07-1258415S0014-5793(10)X0014-XResearch Letters with SDA33173322http://www.febsletters.org/article/PIIS0014579310005685/abstract?rss=yesAbstract: The full-length pro-survival protein Mcl-1 predominantly resides on the outer membrane of mitochondria. Here, we identified a mitochondrial matrix-localized isoform of Mcl-1 that lacks 33 amino acid residues at the N-terminus which serve both as a mitochondrial targeting and processing signal. Ectopically-expressed Mcl-1 without the N-terminal 33 residues failed to enter the mitochondrial matrix but retained wt-like activities both for interaction with BH3-only proteins and anti-apoptosis. In contrast, the mitochondrial matrix-localized isoform failed to interact with BH3-only proteins and manifested an attenuated anti-apoptotic activity. This study reveals that import of Mcl-1 into the mitochondrial matrix results in the attenuation of Mcl-1’s anti-apoptotic function.Structured summary: MINT-7965637: NOXA (uniprotkb:Q9JM54) physically interacts (MI:0915) with Mcl-1 (uniprotkb:P97287) by anti tag coimmunoprecipitation (MI:0007)MINT-7965699: Mcl-1 (uniprotkb:P97287) physically interacts (MI:0915) with Bim (uniprotkb:O43521) by anti bait coimmunoprecipitation (MI:0006)MINT-7965655: Mcl-1 (uniprotkb:P97287) physically interacts (MI:0915) with NOXA (uniprotkb:Q9JM54) by anti bait coimmunoprecipitation (MI:0006)MINT-7965711: Bim (uniprotkb:O43521) physically interacts (MI:0915) with Mcl-1 (uniprotkb:P97287) by anti tag coimmunoprecipitation (MI:0007)MINT-7965673: PUMA (uniprotkb:Q9BXH1) physically interacts (MI:0915) with Mcl-1 (uniprotkb:P97287) by anti tag coimmunoprecipitation (MI:0007)MINT-7965685: Mcl-1 (uniprotkb:P97287) physically interacts (MI:0915) with PUMA (uniprotkb:Q9BXH1) by anti bait coimmunoprecipitation (MI:0006)The fast-mobility isoform of mouse Mcl-1 is a mitochondrial matrix-localized protein with attenuated anti-apoptotic activityChi-Ruei Huang, Hsin-Fang Yang-Yen10.1016/j.febslet.2010.07.013FEBS Letters 584, 15 (2010)2010-07-12FEBS Letters2010-07-1258415S0014-5793(10)X0014-XResearch Letters with SDA33233330http://www.febsletters.org/article/PIIS0014579310004916/abstract?rss=yesAbstract: Here we present the first isolation of major histocompatibility complex (MHC) class I genes from two ancient fish, paddlefish (Polyodon spathula) and Chinese sturgeon (Acipenser sinensis). Seventeen sequences obtained showed high polymorphism and positive natural selection with dN/dS>1. Evolutionary relationships revealed that sequences from paddlefish and Chinese sturgeon distinguished from other vertebrate class I and had an intermingling of alleles, which indicates that Acipenseriformes have a common ancestral gene of class I and a trans-species polymorphism across Acipenseriformes. We also found clear evidence of recombination among class I genes of paddlefish and Chinese sturgeon.Evolution of MHC class I genes in two ancient fish, paddlefish (Polyodon spathula) and Chinese sturgeon (Acipenser sinensis)Dengqiang Wang, Lei Zhong, Qiwei Wei, Xiaoni Gan, Shunping He10.1016/j.febslet.2010.05.065FEBS Letters 584, 15 (2010)2010-06-11FEBS Letters2010-06-1158415S0014-5793(10)X0014-XResearch Letters33313339http://www.febsletters.org/article/PIIS0014579310005053/abstract?rss=yesAbstract: The 2-oxoglutarate and iron dependent dioxygenase family are crucial for cellular adaptation to changes in oxygen concentration. We found that cells with OGFOD1 gene silencing in this family showed resistance to cell death under ischemia, and cDNA microarray analysis of OGFOD1 knockout human cells revealed downregulation of ATPAF1. Although reintroduction of the OGFOD1 wild-type gene to OGFOD1 KO cells restored ATPAF1 mRNA levels, the catalytically inactive OGFOD1 mutants did not. Furthermore, introduction of ATPAF1 gene to OGFOD1 KO cells induced ischemic cell death. Thus, OGFOD1 plays an important role in ischemic cell survival and an OGFOD1 iron binding residue is required for ATPAF1 gene expression.OGFOD1, a member of the 2-oxoglutarate and iron dependent dioxygenase family, functions in ischemic signalingKen Saito, Noritaka Adachi, Hideki Koyama, Masayuki Matsushita10.1016/j.febslet.2010.06.015FEBS Letters 584, 15 (2010)2010-06-18FEBS Letters2010-06-1858415S0014-5793(10)X0014-XResearch Letters33403347http://www.febsletters.org/article/PIIS0014579310005107/abstract?rss=yesAbstract: Light chain-associated (AL) amyloidosis is characterized by dominant fibril deposition of the variable domain (VL) of an immunoglobulin light chain, and thus its constant domain (CL) has been considered not to be amyloidogenic. We examined the in vitro fibril formation of the isolated CL in comparison with β2-microglobulin (β2-m), an immunoglobulin domain-like amyloidogenic protein responsible for dialysis-related amyloidosis. Two methods useful for β2-m at neutral pH also induced amyloid fibrils of CL, which were monitored by thioflavin-T binding and electron microscopy (EM). These results suggest that CL plays an important role, more than previously assumed, in the development of AL-amyloidosis.The amyloid fibrils of the constant domain of immunoglobulin light chainKaori Yamamoto, Hisashi Yagi, Young-Ho Lee, József Kardos, Yoshihisa Hagihara, Hironobu Naiki, Yuji Goto10.1016/j.febslet.2010.06.019FEBS Letters 584, 15 (2010)2010-06-18FEBS Letters2010-06-1858415S0014-5793(10)X0014-XResearch Letters33483353http://www.febsletters.org/article/PIIS0014579310005120/abstract?rss=yesAbstract: The nucleic acid sequence at the positions 1067817–1066321 of Pseudomonas aeruginosa PAO1 genome was predicted to encode a novel S-type pyocin, designated S5, based on the genome sequence. However, its antimicrobial spectrum, activity and mechanism have not been investigated. Herein, we report that pyocin S5 has an antimicrobial activity against seven clinical P. aeruginosa isolates (DWW3, InA, InB, In3, In4, In7, and In8). Among them, DWW3 is most sensitive with a minimum inhibitory concentration of 12.6μg/ml and a killing percentage of 95.7 at 225μg/ml. Further, we demonstrated that the antimicrobial mechanism of pyocin S5 is membrane damage, evidenced by the leakage of intracellular materials, the increase of membrane permeability, and cell surface disruption.A predicted S-type pyocin shows a bactericidal activity against clinical Pseudomonas aeruginosa isolates through membrane damageHua Ling, Nazanin Saeidi, Bahareh Haji Rasouliha, Matthew Wook Chang10.1016/j.febslet.2010.06.021FEBS Letters 584, 15 (2010)2010-06-18FEBS Letters2010-06-1858415S0014-5793(10)X0014-XResearch Letters33543358http://www.febsletters.org/article/PIIS001457931000520X/abstract?rss=yesAbstract: Development of neurotrophic peptidergic drugs that can mimic neurotrophins and promote neurogenesis and maturation of newborn cells into mature functional neurons represents an exciting therapeutic opportunity for treatment of Alzheimer disease and other learning and memory disorders as well as enhancing cognition of normal individuals. Here we report the design of a peptidergic compound, Ac-DGGLAG-NH2, called P21, when administered peripherally, enhanced learning as well as both short-term and spatial reference memories of normal adult C57Bl6 mice. P21 induced enhancement of neurogenesis and maturation of newly born neurons in the granular cell layer and subgranular zone of the dentate gyrus.Neurotrophic peptides incorporating adamantane improve learning and memory, promote neurogenesis and synaptic plasticity in miceBin Li, Lukas Wanka, Julie Blanchard, Fei Liu, Muhammad Omar Chohan, Khalid Iqbal, Inge Grundke-Iqbal10.1016/j.febslet.2010.06.025FEBS Letters 584, 15 (2010)2010-06-28FEBS Letters2010-06-2858415S0014-5793(10)X0014-XResearch Letters33593365http://www.febsletters.org/article/PIIS0014579310005132/abstract?rss=yesAbstract: Human arylamine N-acetyltransferase 1 (NAT1) is a xenobiotic-metabolizing enzyme that biotransforms aromatic amine chemicals. We show here that biologically-relevant concentrations of inorganic (Hg2+) and organic (CH3Hg+) mercury inhibit the biotransformation functions of NAT1. Both compounds react irreversibly with the active-site cysteine of NAT1 (half-maximal inhibitory concentration (IC50)=250nM and kinact=1.4×104M−1s−1 for Hg2+ and IC50=1.4μM and kinact=2×102M−1s−1 for CH3Hg+). Exposure of lung epithelial cells led to the inhibition of cellular NAT1 (IC50=3 and 20μM for Hg2+ and CH3Hg+, respectively). Our data suggest that exposure to mercury may affect the biotransformation of aromatic amines by NAT1.The human xenobiotic-metabolizing enzyme arylamine N-acetyltransferase 1 (NAT1) is irreversibly inhibited by inorganic (Hg2+) and organic mercury (CH3Hg+): Mechanism and kineticsNilusha Ragunathan, Florent Busi, Benjamin Pluvinage, Elodie Sanfins, Jean-Marie Dupret, Fernando Rodrigues-Lima, Julien Dairou10.1016/j.febslet.2010.06.022FEBS Letters 584, 15 (2010)2010-06-18FEBS Letters2010-06-1858415S0014-5793(10)X0014-XResearch Letters33663369http://www.febsletters.org/article/PIIS0014579310005211/abstract?rss=yesAbstract: Archaea-specific D-family DNA polymerase forms a heterotetramer consisting of two large polymerase subunits and two small exonuclease subunits. We analyzed the structure of the N-terminal 200 amino-acid regulatory region of the small subunit by NMR and revealed that the N-terminal ∼70 amino-acid region is folded. The structure consists of a four-α-helix bundle including a short parallel β-sheet, which is similar to the N-terminal regions of the B subunits of human DNA polymerases α and ε, establishing evolutionary relationships among these archaeal and eukaryotic polymerases. We observed monomer–dimer equilibrium of this domain, which may be related to holoenzyme architecture and/or functional regulation.Solution structure of the N-terminal domain of the archaeal D-family DNA polymerase small subunit reveals evolutionary relationship to eukaryotic B-family polymerasesKazuhiko Yamasaki, Yuji Urushibata, Tomoko Yamasaki, Fumio Arisaka, Ikuo Matsui10.1016/j.febslet.2010.06.026FEBS Letters 584, 15 (2010)2010-06-23FEBS Letters2010-06-2358415S0014-5793(10)X0014-XResearch Letters33703375http://www.febsletters.org/article/PIIS0014579310005235/abstract?rss=yesAbstract: Barley thioredoxin h isozymes 1 (HvTrxh1) and barley thioredoxin h isozymes 2 (HvTrxh2) show distinct spatiotemporal distribution in germinating seeds. Using a novel approach involving measurement of bidirectional electron transfer rates between Escherichia coli thioredoxin, which exhibits redox-dependent fluorescence, and the barley isozymes, reaction kinetics and thermodynamic properties were readily determined. The reaction constants were ∼60% higher for HvTrxh1 than HvTrxh2, while their redox potentials were very similar. The primary nucleophile, CysN, of the active site Trp-CysN-Gly-Pro-CysC motif has an apparent pKa of 7.6 in both isozymes, as found by iodoacetamide titration, but showed ∼70% higher reactivity in HvTrxh1, suggesting significant functional difference between the isozymes.Kinetic and thermodynamic properties of two barley thioredoxin h isozymes, HvTrxh1 and HvTrxh2Kenji Maeda, Per Hägglund, Olof Björnberg, Jakob R. Winther, Birte Svensson10.1016/j.febslet.2010.06.028FEBS Letters 584, 15 (2010)2010-06-23FEBS Letters2010-06-2358415S0014-5793(10)X0014-XResearch Letters33763380http://www.febsletters.org/article/PIIS0014579310005272/abstract?rss=yesAbstract: Integrins and syndecans mediate cell adhesion to extracellular matrix and their synergistic cooperation is implicated in cell adhesion processes. We previously identified two active peptides, AG73 and EF1, from the laminin α1 chain LG4 module, that promote cell attachment through syndecan- and α2β1 integrin-binding, respectively. Here, we examined time-dependent cell attachment on the mixed peptides AG73/EF1. The AG73/EF1 promoted stronger and more rapid cell attachment, spreading, FAK phosphorylation that reached a maximum at 20min than that on AG73 (40min) or EF1 (90min) supplied singly. Thus, the syndecan- and α2β1 integrin-binding peptides synergistically affect cells and accelerate cell adhesion.Syndecan- and integrin-binding peptides synergistically accelerate cell adhesionKentaro Hozumi, Kazuki Kobayashi, Fumihiko Katagiri, Yamato Kikkawa, Yuichi Kadoya, Motoyoshi Nomizu10.1016/j.febslet.2010.06.032FEBS Letters 584, 15 (2010)2010-06-24FEBS Letters2010-06-2458415S0014-5793(10)X0014-XResearch Letters33813385http://www.febsletters.org/article/PIIS0014579310005259/abstract?rss=yesAbstract: African horse sickness virus (AHSV), a member of the orbivirus genus of the family Reoviridae, is an insect-vectored pathogen of horses of concern to the equine industry. Studies on AHSV replication and pathogenesis have been hampered by the lack of reverse genetics allowing targeted mutation of viral genomes. We demonstrate that AHSV single-stranded RNA synthesized in vitro (core transcripts) is infectious and that there are distinct primary and secondary stages of the replication cycle. Transfection with a mixture of core transcripts from two different serotypes or a mixture of core transcripts and a T7 derived transcript resulted in the recovery of reassortant viruses. Recovery of infectious ASHV from nucleic acid will benefit investigation of the virus and the generation of attenuated vaccines.A reverse genetics system of African horse sickness virus reveals existence of primary replicationEiko Matsuo, Cristina C.P. Celma, Polly Roy10.1016/j.febslet.2010.06.030FEBS Letters 584, 15 (2010)2010-06-24FEBS Letters2010-06-2458415S0014-5793(10)X0014-XResearch Letters33863391http://www.febsletters.org/article/PIIS0014579310005284/abstract?rss=yesAbstract: Breast cancer resistance protein (BCRP) has been shown to confer multidrug resistance, but the mechanisms of its regulation are poorly understood. Here, we investigate the effects of wild-type and mutant p53, and nuclear factor kappa-B (NF-κB) (p50) on BCRP promoter activity in MCF-7 cells. Our results demonstrated that wild-type p53 markedly suppressed BCRP activity and enhanced the chemosensitivity of cells to mitoxantrone, whereas mutant p53 had little inhibitory effect. After inhibition of NF-κB, similar results were obtained. Following knockdown of endogenous p53, BCRP and p50 expressions were increased, and the chemosensitivity of the cells to mitoxantrone was decreased. We conclude that wild-type p53 acts as a negative regulator of BCRP gene transcription.Transcriptional suppression of breast cancer resistance protein (BCRP) by wild-type p53 through the NF-κB pathway in MCF-7 cellsXuedong Wang, Xingang Wu, Chengkun Wang, Weijia Zhang, Yongmei Ouyang, Yanhui Yu, Zhimin He10.1016/j.febslet.2010.06.033FEBS Letters 584, 15 (2010)2010-06-28FEBS Letters2010-06-2858415S0014-5793(10)X0014-XResearch Letters33923397http://www.febsletters.org/article/PIIS0014579310005296/abstract?rss=yesAbstract: Overexpression of thioredoxin (TRX) confers oxidative stress resistance and extends lifespan in mammals and insects. However, less is known about phenotypes associated with loss of TRX. We investigated loss-of-function phenotypes of Trx-2 in Drosophila, and found that the mutant flies are hyper-susceptible to paraquat, a free radical generator, but not to hydrogen peroxide. They contain a high amount of protein carbonyl, which dramatically increases with age. Trx-2 mutants express high levels of anti-oxidant genes, such as superoxide dismutase, catalase, and glutathione synthetase. This is the first demonstration of biochemical and physiological consequences caused by loss of Trx-2 in Drosophila.Loss of Trx-2 enhances oxidative stress-dependent phenotypes in DrosophilaManabu Tsuda, Ryousuke Ootaka, Chiaki Ohkura, Yoshihito Kishita, Ki-Hyeon Seong, Takashi Matsuo, Toshiro Aigaki10.1016/j.febslet.2010.06.034FEBS Letters 584, 15 (2010)2010-06-28FEBS Letters2010-06-2858415S0014-5793(10)X0014-XResearch Letters33983401http://www.febsletters.org/article/PIIS0014579310005314/abstract?rss=yesAbstract: Mitochondrial energy production is involved in various cellular processes. Here we show that ATP content is significantly increased in lineage-restricted progenitor cells compared with hematopoietic stem and progenitor cells (HSPCs) or more differentiated cells. Transplantation analysis using a mouse model of mitochondrial disease revealed that mitochondrial respiration defects resulted in a significant decrease in the total number and repopulating activity of bone marrow cells, although the number of HSPCs increased. The proliferative activity of HSPCs and lineage-restricted progenitor cells was not impaired by reduction of ATP content and there seems to be no associated increase in reactive oxygen species levels and apoptosis. Our findings indicate that mitochondrial respiration defects modulate HSPC commitment/differentiation into lineage-restricted progenitor cells.Mitochondrial respiration defects modulate differentiation but not proliferation of hematopoietic stem and progenitor cellsShin-Ichi Inoue, Shinichi Noda, Koutarou Kashima, Kazuto Nakada, Jun-Ichi Hayashi, Hiroyuki Miyoshi10.1016/j.febslet.2010.06.036FEBS Letters 584, 15 (2010)2010-06-29FEBS Letters2010-06-2958415S0014-5793(10)X0014-XResearch Letters34023409http://www.febsletters.org/article/PIIS0014579310005338/abstract?rss=yesAbstract: β-Amyloid peptide (Aβ) is generated via sequential proteolysis of amyloid precursor protein (APP) by β- and γ-secretases. Cell-based screening experiments disclosed that the MEK (MAP kinase kinase) inhibitors, U0126 and PD184352, suppress Aβ secretion from human neuronal SH-SY5Y cells expressing Swedish mutant APP. These inhibitors did not affect the cellular levels of APP but significantly reduced those of the APP β-C-terminal fragment (β-CTF). Additionally, β-CTF levels were markedly reduced by these inhibitors in cells expressing the fragment in a γ-secretase-independent and proteasome-dependent manner. Our results suggest that MEK inhibitors reduce Aβ generation via secretase-independent alteration of β-CTF levels.MEK inhibitors suppress β-amyloid production by altering the level of a β-C-terminal fragment of amyloid precursor protein in neuronal cellsWataru Araki, Fuyuki Kametani, Akiko Oda, Akira Tamaoka10.1016/j.febslet.2010.06.038FEBS Letters 584, 15 (2010)2010-06-30FEBS Letters2010-06-3058415S0014-5793(10)X0014-XResearch Letters34103414http://www.febsletters.org/article/PIIS0014579310005387/abstract?rss=yesAbstract: Angiogenesis is a physiological process involving the growth of blood vessel in response to specific stimuli. The present study shows that limited microgravity treatments induce angiogenesis by activating macrovascular endothelial cells. Inhibition of nitric oxide production using pharmacological inhibitors and inducible nitric oxide synthase (iNOS) small interfering ribo nucleic acid (siRNA) abrogated microgravity induced nitric oxide production in macrovascular cells. The study further delineates that iNOS acts as a molecular switch for the heterogeneous effects of microgravity on macrovascular, endocardial and microvascular endothelial cells. Further dissection of nitric oxide downstream signaling confirms that simulated microgravity induces angiogenesis via the cyclic guanosine monophosphate (cGMP)–PKG dependent pathway.Simulated microgravity promotes nitric oxide-supported angiogenesis via the iNOS–cGMP–PKG pathway in macrovascular endothelial cellsJamila H. Siamwala, Syamantak Majumder, K.P. Tamilarasan, Ajit Muley, Seerapu H. Reddy, Gopi Krishna Kolluru, Swaraj Sinha, Suvro Chatterjee10.1016/j.febslet.2010.06.039FEBS Letters 584, 15 (2010)2010-07-01FEBS Letters2010-07-0158415S0014-5793(10)X0014-XResearch Letters34153423http://www.febsletters.org/article/PIIS0014579310005399/abstract?rss=yesAbstract: Several mRNAs are known to be targeted to dendrites in hippocampal neurons. In this study, we show that brain-derived neurotrophic factor (BDNF) mRNA has two distinct cis-acting dendritic targeting elements in the short 3′ untranslated region (UTR): a constitutive element and an activity-dependent one. Moreover, deletion of serial cytoplasmic polyadenylation element (CPE)-like sequences in the short 3′UTR suppressed both constitutive and activity-dependent dendritic targeting. In addition to the interaction with cytoplasmic polyadenylation element binding protein-1 (CPEB-1), depolarization enhanced CPEB-1 recruitment to the activity-dependent targeting element. These results suggest that CPE-like sequences are involved in the activity-dependent as well as constitutive dendritic targeting of BDNF mRNA.Cytoplasmic polyadenylation element-like sequences are involved in dendritic targeting of BDNF mRNA in hippocampal neuronsSouichi Oe, Yoshihiro Yoneda10.1016/j.febslet.2010.06.040FEBS Letters 584, 15 (2010)2010-07-05FEBS Letters2010-07-0558415S0014-5793(10)X0014-XResearch Letters34243430http://www.febsletters.org/article/PIIS0014579310005405/abstract?rss=yesAbstract: Cel9A from the thermoacidophilic bacterium Alicyclobacillus acidocaldarius belongs to the subfamily E1 of family 9 glycoside hydrolases, many members of which have an N-terminal Ig-like domain followed by the catalytic domain. The Ig-like domain is not directly involved in either carbohydrate binding or biocatalysis; however, deletion of the Ig-domain promotes loss of enzymatic activity. We have investigated the functional role of the Ig-like domain using molecular dynamics simulations. Our simulations indicate that residues within the Ig-like domain are dynamically correlated with residues in the carbohydrate-binding pocket and with key catalytic residues of Cel9A. Free energy perturbation simulations indicate that the Ig-like domain stabilizes the catalytic domain and may be responsible for the enhanced thermostability of Cel9A.Molecular simulations provide new insights into the role of the accessory immunoglobulin-like domain of Cel9AHanbin Liu, Jose Henrique Pereira, Paul D. Adams, Rajat Sapra, Blake A. Simmons, Kenneth L. Sale10.1016/j.febslet.2010.06.041FEBS Letters 584, 15 (2010)2010-07-05FEBS Letters2010-07-0558415S0014-5793(10)X0014-XResearch Letters34313435http://www.febsletters.org/article/PIIS0014579310005417/abstract?rss=yesAbstract: Maturation of some snoRNAs is dependent on RNase III-like endonuclease-mediated transcript cleavage, which serves as an entry for the nuclear exosome complex that trims the transcript at the 3′-end. Sequence deletions suggest this cleavage in the U3 snoRNA transcripts of Schizosaccharomyces pombe can induce transcript termination. Using mutational analyses, we demonstrate that the degree of cleavage correlates closely with both RNA maturation and transcript termination. We also show that the RNase III-like endonuclease, Pac1, and the nuclear 5′-exonuclease, Dhp1p, are essential for RNA production and transcript termination, supporting a “reversed torpedoes” model in which the endonuclease cut allows 5′- and 3′-exonuclease activities access to the transcript, leading simultaneously to transcript termination in one direction and RNA maturation in the other.Pac1 endonuclease and Dhp1p 5′→3′ exonuclease are required for U3 snoRNA termination in Schizosaccharomyces pombeSadeq Nabavi, Ross N. Nazar10.1016/j.febslet.2010.06.042FEBS Letters 584, 15 (2010)2010-07-05FEBS Letters2010-07-0558415S0014-5793(10)X0014-XResearch Letters34363441http://www.febsletters.org/article/PIIS0014579310005429/abstract?rss=yesAbstract: The geometry of the axial ligands of the hemes in the triheme cytochrome PpcA from Geobacter sulfurreducens was determined in solution for the ferric form using the unambiguous assignment of the NMR signals of the α-substituents of the hemes. The paramagnetic 13C shifts of the hemes can be used to define the heme electronic structure, the geometry of the axial ligands, and the magnetic susceptibility tensor. The latter establishes the magnitude and geometrical dependence of the pseudocontact shifts, which are crucial to warrant reliable structural constraints for a detailed structural characterization of this paramagnetic protein in solution.Orientation of the axial ligands and magnetic properties of the hemes in the triheme ferricytochrome PpcA from G. sulfurreducens determined by paramagnetic NMRLeonor Morgado, Ivo H. Saraiva, Ricardo O. Louro, Carlos A. Salgueiro10.1016/j.febslet.2010.06.043FEBS Letters 584, 15 (2010)2010-07-05FEBS Letters2010-07-0558415S0014-5793(10)X0014-XResearch Letters34423445http://www.febsletters.org/article/PIIS0014579310005508/abstract?rss=yesAbstract: Leukotriene A4 hydrolase (LTA4H) is a key enzyme in the inflammatory process of mammals. It is an epoxide hydrolase and an aminopeptidase of the M1 family of the MA clan of Zn-metallopeptidases. We have solved the crystal structure of LTA4H in complex with N-[3(R)-[(hydroxyamino)carbonyl]-2-benzyl-1-oxopropyl]-L-alanine, a potent inhibitor of several Zn-metalloenzymes, both endopeptidases and aminopeptidases. The inhibitor binds along the sequence signature for M1 aminopeptidases, GXMEN. It exhibits bidentate chelation of the catalytic zinc and binds to LTA4H’s enzymatically essential carboxylate recognition site. The structure gives clues to the binding of this inhibitor to related enzymes and thereby identifies residues of their S1′ sub sites as well as strategies for design of inhibitors.Crystal structure of leukotriene A4 hydrolase in complex with kelatorphan, implications for design of zinc metallopeptidase inhibitorsFredrik Tholander, Bernard-Pierre Roques, Marie-Claude Fournié-Zaluski, Marjolein M.G.M. Thunnissen, Jesper Z. Haeggström10.1016/j.febslet.2010.06.044FEBS Letters 584, 15 (2010)2010-07-05FEBS Letters2010-07-0558415S0014-5793(10)X0014-XResearch Letters34463451http://www.febsletters.org/article/PIIS001457931000551X/abstract?rss=yesAbstract: Dicer is a ribonuclease playing a key role in the biogenesis of microRNAs and small interfering RNAs. Here we report the identification of a novel splice variant of human dicer gene, the first one bearing a modified coding sequence. It encodes a truncated protein, t-Dicer that lacks the dsRNA-binding domain and is defective in one of the two RNase III catalytic centers. The splice variant was found in neuroblastoma cells and in cells induced to neuronal differentiation, whereas it was not detectable in other cell lines or in normal tissues. Interestingly, it occurred in primary neuroblastic tumors, mainly in stroma poor neuroblastomas.A novel splice variant of the human dicer gene is expressed in neuroblastoma cellsNicoletta Potenza, Umberto Papa, Paola Scaruffi, Nicola Mosca, Gian Paolo Tonini, Aniello Russo10.1016/j.febslet.2010.06.045FEBS Letters 584, 15 (2010)2010-07-06FEBS Letters2010-07-0658415S0014-5793(10)X0014-XResearch Letters34523457http://www.febsletters.org/article/PIIS0014579310005545/abstract?rss=yesAbstract: Tobacco SABP2, a 29kDa protein catalyzes the conversion of methyl salicylic acid (MeSA) into salicylic acid (SA) to induce SAR. Pretreatment of plants with acibenzolar-S-methyl (ASM), a functional analog of salicylic acid induces systemic acquired resistance (SAR). Data presented in this paper suggest that SABP2 catalyzes the conversion of ASM into acibenzolar to induce SAR. Transgenic SABP2-silenced tobacco plants when treated with ASM, fail to express PR-1 proteins and do not induce robust SAR expression. When treated with acibenzolar, full SAR is induced in SABP2-silenced plants. These results show that functional SABP2 is required for ASM-mediated induction of resistance.SABP2, a methyl salicylate esterase is required for the systemic acquired resistance induced by acibenzolar-S-methyl in plantsDiwaker Tripathi, Yu-Lin Jiang, Dhirendra Kumar10.1016/j.febslet.2010.06.046FEBS Letters 584, 15 (2010)2010-07-09FEBS Letters2010-07-0958415S0014-5793(10)X0014-XResearch Letters34583463http://www.febsletters.org/article/PIIS0014579310005570/abstract?rss=yesAbstract: The pKa value of Lys115, the catalytic residue in acetoacetate decarboxylate, was calculated using atomic coordinates of the X-ray crystal structure with consideration of the protonation states of all titratable sites in the protein. The calculated pKa value of Lys115 (pKa(Lys115)) was unusually low (≈6) in agreement with the experimentally measured value. Although charged residues impact pKa(Lys115) considerably in the native protein, the significant pKa(Lys115) downshift in the protein with respect to aqueous solution was mainly due to loss of the solvation energy in the catalytic active site relative to bulk water.Origin of the pKa shift of the catalytic lysine in acetoacetate decarboxylaseHiroshi Ishikita10.1016/j.febslet.2010.07.003FEBS Letters 584, 15 (2010)2010-07-09FEBS Letters2010-07-0958415S0014-5793(10)X0014-XResearch Letters34643468http://www.febsletters.org/article/PIIS0014579310005600/abstract?rss=yesAbstract: Very low density lipoprotein receptors (VLDLR) including type I and type II are known to affect cell functions by binding to its extracellular ligands. However, the effect of these ligands on VLDLR expression remains elusive. Tissue factor pathway inhibitor (TFPI) and urokinase plasminogen activator and plasminogen activator inhibitor 1 (uPA–PAI-1) complex, two ligands of VLDLR, were used to examine their effects on VLDLR expression. TFPI treatment decreased type II VLDLR expression, inhibited cell proliferation and migration, and degradated β-catenin in SGC7901 cells. However, uPA–PAI-1 complex, increased type II VLDLR expression with promoted cell proliferation and migration and stabilization of β-catenin. These results indicated that extracellular ligands can change the expression of type II VLDLR to affect cell proliferation and migration.TFPI or uPA–PAI-1 complex affect cell function through expression variation of type II very low density lipoprotein receptorYong Di, Zhiguo Liu, Jun Tian, Yiqiang Zong, Pu Yang, Shen Qu10.1016/j.febslet.2010.07.005FEBS Letters 584, 15 (2010)2010-07-12FEBS Letters2010-07-1258415S0014-5793(10)X0014-XResearch Letters34693473http://www.febsletters.org/article/PIIS0014579310005594/abstract?rss=yesAbstract: Mutagenesis directed to a specific glycosylation site has been widely used to examine biological roles of individual glycans. However, occurrence of any post-translational modification on such deglycosylated mutants has not yet been well characterized. Here we performed mass spectrometric analyses of the Fc fragment of an unglycosylated mutant of mouse immunoglobulin G2b, whose conserved N-glycosylation site, i.e. Asn297, was substituted with alanine. We found that a major part of this mutant is sulfated at Tyr296, which adjacently precedes the originally glycosylated site. Our findings demonstrate that mutational deglycosylation can induce an unexpected post-translational modification in the protein.Mutational deglycosylation of the Fc portion of immunoglobulin G causes O-sulfation of tyrosine adjacently preceding the originally glycosylated siteKatsuyoshi Masuda, Yoshiki Yamaguchi, Noriko Takahashi, Royston Jefferis, Koichi Kato10.1016/j.febslet.2010.07.004FEBS Letters 584, 15 (2010)2010-07-09FEBS Letters2010-07-0958415S0014-5793(10)X0014-XResearch Letters34743479http://www.febsletters.org/article/PIIS001457931000565X/abstract?rss=yesAbstract: Excessive reactive oxygen species (ROS) play a key role in the pathogenesis of diabetic nephropathy. The thioredoxin (TRX) system, a major thiol antioxidant system, regulates the reduction of intracellular ROS. Here we show that high glucose (HG) inhibits TRX ROS-scavenging function through p38 mitogen-activated protein kinase (MAPK)-mediated induction of thioredoxin interacting protein (TXNIP) in mouse mesangial cells (MMCs). Knockdown of TXNIP in MMCs reversed HG-induced reduction of TRX activity and inhibited HG-induced activation of p38 MAPK and increased synthesis of TGF-β1 and fibronectin. These data suggest that HG-induced overexpression of TXNIP in MMCs, which may be via the p38 MAPK pathway.p38 MAPK pathway is involved in high glucose-induced thioredoxin interacting protein induction in mouse mesangial cellsYunzhuo Ren, Yonghong Shi, Yuehua Wang, Yingmin Li, Shuhui Wu, Hang Li, Yanling Zhang, Huijun Duan10.1016/j.febslet.2010.07.010FEBS Letters 584, 15 (2010)2010-07-12FEBS Letters2010-07-1258415S0014-5793(10)X0014-XResearch Letters34803485http://www.febsletters.org/article/PIIS0014579310005661/abstract?rss=yesAbstract: To examine the role of two light chains (LCs) of the myosin II on Ca2+ regulation, we produced hybrid heavy meromyosin (HMM) having LCs from Physarum and/or scallop myosin using the smooth muscle myosin heavy chain. Ca2+ inhibited motility and ATPase activity of hybrid HMMs with LCs from Physarum myosin but activated those of hybrid HMM with LCs from scallop myosin, indicating an active role of LCs. ATPase activity of hybrid HMMs with LCs from different species showed the same effect by Ca2+ even though they did not support motility. Our results suggest that communication between the original combinations of LC is important for the motor function.Calcium regulation of the ATPase activity of Physarum and scallop myosins using hybrid smooth muscle myosin: The role of the essential light chainYing Zhang, Akio Nakamura, Hozumi Kawamichi, Shinji Yoshiyama, Takeshi Katayama, Kazuhiro Kohama10.1016/j.febslet.2010.07.011FEBS Letters 584, 15 (2010)2010-07-13FEBS Letters2010-07-1358415S0014-5793(10)X0014-XResearch Letters34863491http://www.febsletters.org/article/PIIS0014579310005648/abstract?rss=yesAbstract: We previously showed that cAMP can inhibit DNA damage-induced wild type p53 accumulation in human pre-B NALM-6 cells, leading to a profound reduction of their apoptotic response. Here, we provide evidence for the potentiation of DNA damage-induced NF-κB activation by cAMP. We found that inhibition of NF-κB activation prevents the inhibitory effect of cAMP on doxorubicin-induced apoptosis. Moreover, cAMP exerts its inhibitory effect on doxorubicin-induced apoptosis in a PKA-independent manner. The present study also shows that elevation of cAMP prolongs the phosphorylation of IκB and subsequent activation of NF-κB in doxorubicin treated NALM-6 cells in a proteasome-dependent manner. Taken together, our results demonstrate that cAMP abrogates the balance between apoptotic and antiapoptotic transcription factors that are hallmarks of DNA damage signaling.Elevation of cyclic AMP causes an imbalance between NF-κB and p53 in NALM-6 cells treated by doxorubicinMajid Safa, Hamid Zand, Kazem Mousavizadeh, Ahmad Kazemi, Masoumeh Bakhshayesh, Parisa Hayat10.1016/j.febslet.2010.07.009FEBS Letters 584, 15 (2010)2010-07-12FEBS Letters2010-07-1258415S0014-5793(10)X0014-XResearch Letters34923498http://www.febsletters.org/article/PIIS0014579310005703/abstract?rss=yesAbstract: AMP-activated protein kinase (AMPK) is a heterotrimer of catalytic (α) and regulatory (β and γ) subunits with at least two isoforms for each subunit. AMPK β1 is widely expressed whilst AMPK β2 is highly expressed in muscle and both β isoforms contain a mid-molecule carbohydrate-binding module (β-CBM). Here we show that β2-CBM has evolved to contain a Thr insertion and increased affinity for glycogen mimetics with a preference for oligosaccharides containing a single α-1,6 branched residue. Deletion of Thr-101 reduces affinity for single α-1,6 branched oligosaccharides by 3-fold, while insertion of this residue into the equivalent position in the β1-CBM sequence increases affinity by 3-fold, confirming the functional importance of this residue.AMPK β subunits display isoform specific affinities for carbohydratesAnn Koay, Ben Woodcroft, Emma J. Petrie, Helen Yue, Shane Emanuelle, Michael Bieri, Michael F. Bailey, Mark Hargreaves, Jong-Tae Park, Kwan-Hwa Park, Stuart Ralph, Dietbert Neumann, David Stapleton, Paul R. Gooley10.1016/j.febslet.2010.07.015FEBS Letters 584, 15 (2010)2010-07-14FEBS Letters2010-07-1458415S0014-5793(10)X0014-XResearch Letters34993503http://www.febsletters.org/article/PIIS0014579310005740/abstract?rss=yesAbstract: Our previous studies indicated that exogenous α-synuclein (ASN) activates neuronal nitric oxide (NO) synthase (nNOS) in rat brain slices. The present study, carried out on immortalized hippocampal neuronal cells (HT22), was designed to extend the previous results by showing the molecular pathway of NO-mediated cell death induced by exogenous ASN. Extracellular ASN (10μM) was found to stimulate nitric oxide synthase (NOS) and increase caspase-3 activity in HT22 cells, leading to poly(ADP-ribose) polymerase (PARP-1) cleavage. The inhibitor of Ca2+-dependent NOS (N-nitro-l-arginine, 100μM) prevented ASN-evoked caspase-3 activation and PARP-1 degradation. ASN exposure resulted in apoptotic death of HT22 cells and this effect was reversed by inhibition of NO synthesis and caspase-3 activity. Our results demonstrated that extracellular ASN induces neuronal cell death by NO-mediated caspase-3 activation.α-Synuclein induced cell death in mouse hippocampal (HT22) cells is mediated by nitric oxide-dependent activation of caspase-3Agata Adamczyk, Anna Kaźmierczak, Grzegorz Arkadiusz Czapski, Joanna Benigna Strosznajder10.1016/j.febslet.2010.07.019FEBS Letters 584, 15 (2010)2010-07-16FEBS Letters2010-07-1658415S0014-5793(10)X0014-XResearch Letters35043508