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10.1128/MCB.00595-14 http://scihub22266oqcxt.onion/10.1128/MCB.00595-14 C4187722!4187722 !25047832     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25047832 &cmd=llinks): Failed to open stream: HTTP request failed! 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Cyclin-dependent kinase 7 controls mRNA synthesis by affecting stability of preinitiation complexes, leading to altered gene expression, cell cycle progression, and survival of tumor cells |pdf=|usr=}}{{25047832 }} gab.com Text Cyclin-dependent kinase 7 controls mRNA synthesis by affecting stability of preinitiation complexes, leading to altered gene expression, cell cycle progression, and survival of tumor cells JO: Mol Cell Biol http://www.kidney.de/pget.php?&tw=1&pmid=25047832 #FOAvip Cyclin-dependent kinase 7 (CDK7) activates cell cycle CDKs and is a member of the general transcription factor TFIIH. Although there is substantial evidence for an active role of CDK7 in mRNA synthesis and associated processes, the degree of its influence on global and gene-specific transcription in mammalian species is unclear. In the current study, we utilize two novel inhibitors with high specificity for CDK7 to demonstrate a restricted but robust impact of CDK7 on gene transcription in vivo and in in vitro-reconstituted reactions. We distinguish between relative low- and high-dose responses and relate them to distinct molecular mechanisms and altered physiological responses. Low inhibitor doses cause rapid clearance of paused RNA polymerase II (RNAPII) molecules and sufficed to cause genome-wide alterations in gene expression, delays in cell cycle progression at both the G1/S and G2/M checkpoints, and diminished survival of human tumor cells. Higher doses and prolonged inhibition led to strong reductions in RNAPII carboxyl-terminal domain (CTD) phosphorylation, eventual activation of the p53 program, and increased cell death. Together, our data reason for a quantitative contribution of CDK7 to mRNA synthesis, which is critical for cellular homeostasis. Twit Text FOAVip Cyclin-dependent kinase 7 controls mRNA synthesis by affecting stability of preinitiation complexes, leading to altered gene expression, cell cycle progression, and survival of tumor cells ????Mol Cell Biol http://www.kidney.de/pget.php?&tw=1&pmid=25047832 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25047832 #FOAvip English Wikipedia <ref>{{Cite pmid|25047832 }}</ref> Cyclin-dependent kinase 7 controls mRNA synthesis by affecting stability of preinitiation complexes, leading to altered gene expression, cell cycle progression, and survival of tumor cells #MMPMID25047832 Kelso TW ; Baumgart K ; Eickhoff J ; Albert T ; Antrecht C ; Lemcke S ; Klebl B ; Meisterernst M Mol Cell Biol 2014[Oct]; 34 (19 ): 3675-88 PMID25047832 show ga Cyclin-dependent kinase 7 (CDK7) activates cell cycle CDKs and is a member of the general transcription factor TFIIH. Although there is substantial evidence for an active role of CDK7 in mRNA synthesis and associated processes, the degree of its influence on global and gene-specific transcription in mammalian species is unclear. In the current study, we utilize two novel inhibitors with high specificity for CDK7 to demonstrate a restricted but robust impact of CDK7 on gene transcription in vivo and in in vitro-reconstituted reactions. We distinguish between relative low- and high-dose responses and relate them to distinct molecular mechanisms and altered physiological responses. Low inhibitor doses cause rapid clearance of paused RNA polymerase II (RNAPII) molecules and sufficed to cause genome-wide alterations in gene expression, delays in cell cycle progression at both the G1/S and G2/M checkpoints, and diminished survival of human tumor cells. Higher doses and prolonged inhibition led to strong reductions in RNAPII carboxyl-terminal domain (CTD) phosphorylation, eventual activation of the p53 program, and increased cell death. Together, our data reason for a quantitative contribution of CDK7 to mRNA synthesis, which is critical for cellular homeostasis. |Apoptosis/drug effects [MESH] |Cell Cycle/drug effects [MESH] |Cell Line, Tumor [MESH] |Cyclin-Dependent Kinase-Activating Kinase [MESH] |Cyclin-Dependent Kinases/antagonists & inhibitors/genetics/*metabolism [MESH] |Dose-Response Relationship, Drug [MESH] |Gene Expression Regulation, Neoplastic/drug effects [MESH] |HEK293 Cells [MESH] |HeLa Cells [MESH] |Humans [MESH] |Neoplasms/genetics/*metabolism [MESH] |Phosphorylation [MESH] |Protein Kinase Inhibitors/*pharmacology [MESH] |Purines/*pharmacology [MESH] |Pyrazoles/*pharmacology [MESH] |Pyrimidines/*pharmacology [MESH] |RNA Polymerase II/*metabolism [MESH] |RNA, Messenger/*genetics [MESH] |Roscovitine [MESH]Cyclin-dependent kinase 7 controls mRNA synthesis by affecting stabili(epmc).pdf DeepDyve Pubget Overpricing