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1دورية أكاديمية
المؤلفون: Horvath, Anelia, Pakala, Suresh B., Mudvari, Prakriti, Reddy, Sirigiri Divijendra Natha, Ohshiro, Kazufumi, Casimiro, Sandra, Pires, Ricardo, Fuqua, Suzanne A.W., Toi, Masakazu, Costa, Luis, Nair, Sujit S., Sukumar, Saraswati, Kumar, Rakesh
المصدر: Biochemistry and Molecular Medicine Faculty Publications
مصطلحات موضوعية: Biochemistry, Biophysics, and Structural Biology
الوصف: Using RNA sequencing of triple-negative breast cancer (TNBC), non-TBNC and HER2-positive breast cancer sub-types, here we report novel expressed variants, allelic prevalence and abundance, and coexpression with other variation, and splicing signatures. To reveal the most prevalent variant alleles, we overlaid our findings with cancer- and population-based datasets and validated a subset of novel variants of cancer-related genes: ESRP2, GBP1, TPP1, MAD2L1BP, GLUD2 and SLC30A8. As a proof-of-principle, we demonstrated that a rare substitution in the splicing coordinator ESRP2(R353Q) impairs its ability to bind to its substrate FGFR2 pre-mRNA. In addition, we describe novel SNPs and INDELs in cancer relevant genes with no prior reported association of point mutations with cancer, such as MTAP and MAGED1. For the first time, this study illustrates the power of RNA-sequencing in revealing the variation landscape of breast transcriptome and exemplifies analytical strategies to search regulatory interactions among cancer relevant molecules.
وصف الملف: application/pdf
العلاقة: https://hsrc.himmelfarb.gwu.edu/smhs_biochem_facpubs/113Test; https://hsrc.himmelfarb.gwu.edu/cgi/viewcontent.cgi?article=1114&context=smhs_biochem_facpubsTest
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2دورية أكاديمية
المؤلفون: Li, Da-Qiang, Nair, Sujit S., Ohshiro, Kazufumi, Kumar, Anupam, Nair, Vasudha S., Pakala, Suresh B., Reddy, Sirigiri Divijendra Natha, Gajula, Rajendra P., Eswaran, Jeyanthy, Aravind, L., Kumar, Rakesh
المصدر: Biochemistry and Molecular Medicine Faculty Publications
مصطلحات موضوعية: Adenosine Triphosphatases--metabolism, Chromatin Assembly and Disassembly, DNA Damage, Transcription Factors--metabolism, Biochemistry, Biophysics, and Structural Biology
الوصف: Chromatin dynamics play a central role in maintaining genome integrity, but how this is achieved remains largely unknown. Here, we report that microrchidia CW-type zinc finger 2 (MORC2), an uncharacterized protein with a derived PHD finger domain and a conserved GHKL-type ATPase module, is a physiological substrate of p21-activated kinase 1 (PAK1), an important integrator of extracellular signals and nuclear processes. Following DNA damage, MORC2 is phosphorylated on serine 739 in a PAK1-dependent manner, and phosphorylated MORC2 regulates its DNA-dependent ATPase activity to facilitate chromatin remodeling. Moreover, MORC2 associates with chromatin and promotes gamma-H2AX induction in a PAK1 phosphorylation-dependent manner. Consequently, cells expressing MORC2-S739A mutation displayed a reduction in DNA repair efficiency and were hypersensitive to DNA-damaging agent. These findings suggest that the PAK1-MORC2 axis is critical for orchestrating the interplay between chromatin dynamics and the maintenance of genomic integrity through sequentially integrating multiple essential enzymatic processes.
وصف الملف: application/pdf
العلاقة: https://hsrc.himmelfarb.gwu.edu/smhs_biochem_facpubs/28Test; https://hsrc.himmelfarb.gwu.edu/cgi/viewcontent.cgi?article=1027&context=smhs_biochem_facpubsTest
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3دورية أكاديمية
المؤلفون: Li, Da-Qiang, Pakala, Suresh B., Reddy, Sirigiri Divijendra Natha, Peng, Shaohua, Balasenthil, Seetharaman, Deng, Chu-Xia, Lee, Cheng Chi, Rea, Michael A., Kumar, Rakesh
المصدر: Biochemistry and Molecular Medicine Faculty Publications
مصطلحات موضوعية: Circadian Rhythm--genetics, Gene Expression Regulation, Histone Deacetylases--genetics, Repressor Proteins--genetics, Transcription Factors--genetics, Transcription, Genetic, Biochemistry, Biophysics, and Structural Biology
العلاقة: https://hsrc.himmelfarb.gwu.edu/smhs_biochem_facpubs/110Test; http://www.ncbi.nlm.nih.gov/pubmed?holding=dcgwulib_fft_ndi&dr=abstract&otool=dcgwulib&term=24089055Test
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4دورية أكاديمية
المؤلفون: Pakala, Suresh B., Rayala, Suresh K., Wang, Rui-An, Ohshiro, Kazufumi, Mudvari, Prakriti, Reddy, Sirigiri Divijendra Natha, Zheng, Yi, Pires, Ricardo, Casimiro, Sandra, Pillai, M. Radhakrishna, Costa, Luis, Kumar, Rakesh
المصدر: Biochemistry and Molecular Medicine Faculty Publications
مصطلحات موضوعية: Biochemistry, Biophysics, and Structural Biology
العلاقة: https://hsrc.himmelfarb.gwu.edu/smhs_biochem_facpubs/55Test; http://www.ncbi.nlm.nih.gov/pubmed?holding=dcgwulib_fft_ndi&dr=abstract&otool=dcgwulib&term=23580571Test
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5دورية أكاديمية
المؤلفون: Sankuran, Deivendran, Pakala, Suresh B., Nair, Vasudha S., Reddy, Sirigiri Divijendra Natha, Cyanam, Dinesh, Ha, Ngoc-Han, Li, Da-Qiang, Santhoshkumar, T. R., Pillai, M. Radhakrishna, Kumar, Rakesh
المصدر: Biochemistry and Molecular Medicine Faculty Publications
مصطلحات موضوعية: Antigens, CD44--genetics, CD44--metabolism, Extracellular Matrix Proteins--genetics, Extracellular Matrix Proteins--metabolism, Gene Expression Regulation, Neoplastic, Histone Deacetylases--genetics, Repressor Proteins--genetics, Biochemistry, Biophysics, and Structural Biology
العلاقة: https://hsrc.himmelfarb.gwu.edu/smhs_biochem_facpubs/72Test; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285325Test/
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6دورية أكاديمية
المصدر: Biochemistry and Molecular Medicine Faculty Publications
مصطلحات موضوعية: Cell Cycle Proteins--metabolism, Centromere--metabolism, Kinesin--metabolism, Microtubules--metabolism, p21-Activated Kinases--metabolism, Biochemistry, Biophysics, and Structural Biology
العلاقة: https://hsrc.himmelfarb.gwu.edu/smhs_biochem_facpubs/46Test; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504770Test/
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7دورية أكاديمية
المصدر: Biochemistry and Molecular Medicine Faculty Publications
مصطلحات موضوعية: Histone Deacetylases--metabolism, Neoplasms--enzymology, Nucleosomes--metabolism, Repressor Proteins--metabolism, Biochemistry, Biophysics, and Structural Biology
العلاقة: https://hsrc.himmelfarb.gwu.edu/smhs_biochem_facpubs/8Test; http://www.ncbi.nlm.nih.gov/pubmed?holding=dcgwulib_fft_ndi&dr=abstract&otool=dcgwulib&term=22253283Test
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8دورية أكاديمية
المؤلفون: Marzook, Hezlin, Li, Da-Qiang, Nair, Vasudha S., Mudvari, Prakriti, Reddy, Sirigiri Divijendra Natha, Pakala, Suresh B., Santhoshkumar, T. R., Pillai, M. Radhakrishna, Kumar, Rakesh
المصدر: Biochemistry and Molecular Medicine Faculty Publications
مصطلحات موضوعية: Cell Movement--genetics, Gene Silencing, Histone Deacetylases--metabolism, Repressor Proteins--metabolism, Transcription, Genetic--genetics, Ubiquitin-Protein Ligases--deficiency, Ubiquitin-Protein Ligases--genetics, Biochemistry, Biophysics, and Structural Biology
العلاقة: https://hsrc.himmelfarb.gwu.edu/smhs_biochem_facpubs/9Test; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285335Test/
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9دورية أكاديمية
المؤلفون: Ohshiro, Kazufumi, Rayala, Suresh K., Wigerup, Caroline, Pakala, Suresh B., Natha, Reddy S.Divijendra, Gururaj, Anupama E., Molli, Poonam R., Månsson, Sofie Svensson, Ramezani, Ali, Hawley, Robert G., Landberg, Goran, Lee, Norman H., Kumar, Rakesh
المصدر: Pathology Faculty Publications
مصطلحات موضوعية: Lys 626 acetylation, MTA1, Raf1 activation, Ras, transformation
الوصف: High expression of metastasis-associated protein 1 co-regulator (MTA1), a component of the nuclear remodelling and histone deacetylase complex, has been associated with human tumours. However, the precise role of MTA1 in tumorigenesis remains unknown. In this study, we show that induced levels of MTA1 are sufficient to transform Rat1 fibroblasts and that the transforming potential of MTA1 is dependent on its acetylation at Lys626. Underlying mechanisms of MTA1-mediated transformation include activation of the Ras-Raf pathway by MTA1 but not by acetylation-inactive MTA1; this was due to the repression of G ±i2 transcription, which negatively influences Ras activation. We observed that acetylated MTA1-histone deacetylase (HDAC) interaction was required for the recruitment of the MTA1-HDAC complex to the G ±i2 regulatory element and consequently for the repression of G ±i2 transcription and expression leading to activation of the Ras-Raf pathway. The findings presented in this study provide for the first time-to the best of our knowledge-evidence of acetylation-dependent oncogenic activity of a cancer-relevant gene product. © 2010 European Molecular Biology Organization.
