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Gruner S.M.,Stanford University | Gruner S.M.,Cornell University | Lattman E.E.,Hauptman Woodward Medical Research Institute | Lattman E.E.,The New School | Lattman E.E.,Bio Center
Annual Review of Biophysics | Year: 2015

Next-generation synchrotron radiation sources, such as X-ray free-electron lasers, energy recovery linacs, and ultra-low-emittance storage rings, are catalyzing novel methods of biomolecular microcrystallography and solution scattering. These methods are described and future trends are predicted. Importantly, there is a growing realization that serial microcrystallography and certain cutting-edge solution scattering experiments can be performed at existing storage ring sources by utilizing new technology. In this sense, next-generation sources are serving two distinct functions, namely, provision of new capabilities that require the newer sources and inspiration of new methods that can be performed at existing sources. © Copyright ©2015 by Annual Reviews. All rights reserved. Source


Shin S.H.,Chungbuk National University | Shin S.H.,Bio Center | Kang S.S.,Chungbuk National University
Open Biochemistry Journal | Year: 2013

The transfer of acetyl groups from acetyl coenzyme A to the ε amino group of internal lysine residues is catalyzed by Tip60, which is in the MYST family of nuclear histone acetyltransferases (HATs). The tyrosine phosphorylation of Tip60 seems to be a unique modification. We present evidence that Tip60 is modified on tyrosine 327 by Abl kinase. We show that this causes functional changes in HAT activity and the subcellular localization of TIP60, which forms a complex with Abl kinase. The Tip60 mutation Y327F abolished tyrosine phosphorylation, reduced the inhibition of Tip60 HAT activity, and caused G0-G1 arrest and association with FE65. Thus, our findings for the first time suggested a novel regulation mechanism of Tip60. Regulation was through phosphorylation of tyrosine 327 by Abl tyrosine kinase and depended on environmental conditions, suggesting that the tyrosine residue of Tip60 is important for the activation process. © Shin and Kang. Source


Mickiewicz B.,Bio Center | Shin S.Y.,University of Calgary | Pozzi A.,Vanderbilt University | Vogel H.J.,Bio Center | And 2 more authors.
Journal of Proteome Research | Year: 2016

The risk of developing post-traumatic osteoarthritis (PTOA) following joint injury is high. Furthering our understanding of the molecular mechanisms underlying PTOA and/or identifying novel biomarkers for early detection may help to improve treatment outcomes. Increased expression of integrin α1β1 and inhibition of epidermal growth factor receptor (EGFR) signaling protect the knee from spontaneous OA; however, the impact of the integrin α1β1/EGFR axis on PTOA is currently unknown. We sought to determine metabolic changes in serum samples collected from wild-type and integrin α1-null mice that underwent surgery to destabilize the medial meniscus and were treated with the EGFR inhibitor erlotinib. Following 1H nuclear magnetic resonance spectroscopy, we generated multivariate statistical models that distinguished between the metabolic profiles of erlotinib- versus vehicle-treated mice and the integrin α1-null versus wild-type mouse genotype. Our results show the sex-dependent effects of erlotinib treatment and highlight glutamine as a metabolite that counteracts this treatment. Furthermore, we identified a set of metabolites associated with increased reactive oxygen species production, susceptibility to OA, and regulation of TRP channels in α1-null mice. Our study indicates that systemic pharmacological and genetic factors have a greater effect on serum metabolic profiles than site-specific factors such as surgery. © 2016 American Chemical Society. Source


Sarell C.J.,University College London | Karamanos T.K.,University of Leeds | White S.J.,University of Leeds | Bunka D.H.J.,Bio Center | And 5 more authors.
Journal of Biological Chemistry | Year: 2014

Background: Altering the co-polymerization of proteins into amyloid fibrils provides an opportunity for manipulating fibril assembly.Results: NMR and kinetic analysis showed that an RNA aptamer distinguishes between two highly similar co-aggregating proteins.Conclusion: RNA aptamers are specific and discriminatory probes able to modulate amyloid formation.Significance: Aptamers can be used as tools to differentiate amyloid precursors that are closely related and alter assembly. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Source


Lai D.-P.,Bio Center | Tan S.,Anhui University of Science and Technology | Kang Y.-N.,Bio Center | Wu J.,Shanghai JiaoTong University | And 11 more authors.
Human Molecular Genetics | Year: 2015

Alternative polyadenylation (APA) is an important post-transcriptional modification implicated in many diseases, including cancer. Although extensively characterized, the functional consequence of APA modulation on tumorigenesis remains elusive. Here, we developed a deep sequencing-based approach that specifically profiles 3' termini of polyadenylated RNAs (herein termed 3T-seq) and analyzed APA events in two gastric cancer cell lines and one non-transformed counterpart. Overall, we identified ≥28 000 poly(A) sites, 70% of which are potentially novel. Further, we observed widespread APA-mediated 3' UTR shortening of 513 genes (false discovery rate ≤ 0.05) across gastric cancer genome.We characterized one of these genes, NET1, in detail and found that the shortening of NET1 3' UTR significantly enhances transcriptional activity. Moreover, the NET1 isoform with short 3' UTR promotes cellular migration and invasion in vitro. Collectively, our work provides an effective approach for genome-wide APA site profiling and reveals a link between APA modulation and gastric cancer metastasis. © The Author 2015. Published by Oxford University Press. All rights reserved. Source

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