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10.1016/j.ajhg.2016.09.020 http://scihub22266oqcxt.onion/10.1016/j.ajhg.2016.09.020 C5223033!5223033 !27939638     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=27939638 &cmd=llinks): Failed to open stream: HTTP request failed! 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Proteome-Scale Investigation of Protein Allosteric Regulation Perturbed by Somatic Mutations in 7,000 Cancer Genomes |pdf=|usr=}}{{27939638 }} gab.com Text Proteome-Scale Investigation of Protein Allosteric Regulation Perturbed by Somatic Mutations in 7,000 Cancer Genomes JO: Am J Hum Genet http://www.kidney.de/pget.php?&tw=1&pmid=27939638 #FOAvip The allosteric regulation triggering the protein's functional activity via conformational changes is an intrinsic function of protein under many physiological and pathological conditions, including cancer. Identification of the biological effects of specific somatic variants on allosteric proteins and the phenotypes that they alter during tumor initiation and progression is a central challenge for cancer genomes in the post-genomic era. Here, we mapped more than 47,000 somatic missense mutations observed in approximately 7,000 tumor-normal matched samples across 33 cancer types into protein allosteric sites to prioritize the mutated allosteric proteins and we tested our prediction in cancer cell lines. We found that the deleterious mutations identified in cancer genomes were more significantly enriched at protein allosteric sites than tolerated mutations, suggesting a critical role for protein allosteric variants in cancer. Next, we developed a statistical approach, namely AlloDriver, and further identified 15 potential mutated allosteric proteins during pan-cancer and individual cancer-type analyses. More importantly, we experimentally confirmed that p.Pro360Ala on PDE10A played a potential oncogenic role in mediating tumorigenesis in non-small cell lung cancer (NSCLC). In summary, these findings shed light on the role of allosteric regulation during tumorigenesis and provide a useful tool for the timely development of targeted cancer therapies. Twit Text FOAVip Proteome-Scale Investigation of Protein Allosteric Regulation Perturbed by Somatic Mutations in 7,000 Cancer Genomes ????Am J Hum Genet http://www.kidney.de/pget.php?&tw=1&pmid=27939638 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27939638 #FOAvip English Wikipedia <ref>{{Cite pmid|27939638 }}</ref> Proteome-Scale Investigation of Protein Allosteric Regulation Perturbed by Somatic Mutations in 7,000 Cancer Genomes #MMPMID27939638 Shen Q ; Cheng F ; Song H ; Lu W ; Zhao J ; An X ; Liu M ; Chen G ; Zhao Z ; Zhang J Am J Hum Genet 2017[Jan]; 100 (1 ): 5-20 PMID27939638 show ga The allosteric regulation triggering the protein's functional activity via conformational changes is an intrinsic function of protein under many physiological and pathological conditions, including cancer. Identification of the biological effects of specific somatic variants on allosteric proteins and the phenotypes that they alter during tumor initiation and progression is a central challenge for cancer genomes in the post-genomic era. Here, we mapped more than 47,000 somatic missense mutations observed in approximately 7,000 tumor-normal matched samples across 33 cancer types into protein allosteric sites to prioritize the mutated allosteric proteins and we tested our prediction in cancer cell lines. We found that the deleterious mutations identified in cancer genomes were more significantly enriched at protein allosteric sites than tolerated mutations, suggesting a critical role for protein allosteric variants in cancer. Next, we developed a statistical approach, namely AlloDriver, and further identified 15 potential mutated allosteric proteins during pan-cancer and individual cancer-type analyses. More importantly, we experimentally confirmed that p.Pro360Ala on PDE10A played a potential oncogenic role in mediating tumorigenesis in non-small cell lung cancer (NSCLC). In summary, these findings shed light on the role of allosteric regulation during tumorigenesis and provide a useful tool for the timely development of targeted cancer therapies. |*Proteomics [MESH] |Allosteric Regulation/*genetics [MESH] |Allosteric Site/*genetics [MESH] |Carcinogenesis/genetics [MESH] |Carcinoma, Non-Small-Cell Lung/genetics [MESH] |Cell Line, Tumor [MESH] |Genome, Human/*genetics [MESH] |Humans [MESH] |Kaplan-Meier Estimate [MESH] |Lung Neoplasms/genetics [MESH] |Molecular Targeted Therapy/methods/trends [MESH] |Mutation, Missense/*genetics [MESH] |Neoplasms/*genetics [MESH]Proteome-Scale Investigation of Protein Allosteric Regulation Perturbe(epmc).pdf DeepDyve Pubget Overpricing