CTIP2 is a negative regulator of P-TEFb
The positive transcription elongation factor b (P-TEFb) is involved in physiological and pathological events including inflammation, cancer, AIDS, and cardiac hypertrophy. The balance between its active and inactive form is tightly controlled to ensure cellular integrity. We report that the transcri...
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creator | Cherrier, Thomas Le Douce, Valentin Eilebrecht, Sebastian Riclet, Raphael Marban, Céline Dequiedt, Franck Goumon, Yannick Paillart, Jean-Christophe Mericskay, Mathias Parlakian, Ara Bausero, Pedro Abbas, Wasim Herbein, Georges Kurdistani, Siavash K. Grana, Xavier Van Driessche, Benoit Schwartz, Christian Candolfi, Ermanno Benecke, Arndt G. Van Lint, Carine Rohr, Olivier |
description | The positive transcription elongation factor b (P-TEFb) is involved in physiological and pathological events including inflammation, cancer, AIDS, and cardiac hypertrophy. The balance between its active and inactive form is tightly controlled to ensure cellular integrity. We report that the transcriptional repressor CTIP2 is a major modulator of P-TEFb activity. CTIP2 copurifies and interacts with an inactive P-TEFb complex containing the 7SK snRNA and HEXIM1. CTIP2 associates directly with HEXIM1 and, via the loop 2 of the 7SK snRNA, with P-TEFb. In this nucleoprotein complex, CTIP2 significantly represses the Cdk9 kinase activity of P-TEFb. Accordingly, we show that CTIP2 inhibits large sets of P-TEFb- and 7SK snRNA-sensitive genes. In hearts of hypertrophic cardiomyopathic mice, CTIP2 controls P-TEFb-sensitive pathways involved in the establishment of this pathology. Overexpression of the β-myosin heavy chain protein contributes to the pathological cardiac wall thickening. The inactive P-TEFb complex associates with CTIP2 at the MYH7 gene promoter to repress its activity. Taken together, our results strongly suggest that CTIP2 controls P-TEFb function in physiological and pathological conditions. |
doi_str_mv | 10.1073/pnas.1220136110 |
format | Article |
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The balance between its active and inactive form is tightly controlled to ensure cellular integrity. We report that the transcriptional repressor CTIP2 is a major modulator of P-TEFb activity. CTIP2 copurifies and interacts with an inactive P-TEFb complex containing the 7SK snRNA and HEXIM1. CTIP2 associates directly with HEXIM1 and, via the loop 2 of the 7SK snRNA, with P-TEFb. In this nucleoprotein complex, CTIP2 significantly represses the Cdk9 kinase activity of P-TEFb. Accordingly, we show that CTIP2 inhibits large sets of P-TEFb- and 7SK snRNA-sensitive genes. In hearts of hypertrophic cardiomyopathic mice, CTIP2 controls P-TEFb-sensitive pathways involved in the establishment of this pathology. Overexpression of the β-myosin heavy chain protein contributes to the pathological cardiac wall thickening. The inactive P-TEFb complex associates with CTIP2 at the MYH7 gene promoter to repress its activity. Taken together, our results strongly suggest that CTIP2 controls P-TEFb function in physiological and pathological conditions.</description><identifier>ISSN: 0027-8424</identifier><identifier>ISSN: 1091-6490</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1220136110</identifier><identifier>PMID: 23852730</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Acquired immune deficiency syndrome ; AIDS ; Animals ; Antibodies ; Biochemistry, biophysics & molecular biology ; Biochimie, biophysique & biologie moléculaire ; Biological Sciences ; Cancer ; Cardiac Myosins - genetics ; Cardiac Myosins - metabolism ; Cardiac Myosins/genetics/metabolism ; Cardiomegaly - genetics ; Cardiomegaly - metabolism ; Cardiomegaly - pathology ; Cardiomegaly/genetics/metabolism/pathology ; Cell lines ; Cyclin-Dependent Kinase 9 - genetics ; Cyclin-Dependent Kinase 9 - metabolism ; Cyclin-Dependent Kinase 9/genetics/metabolism ; Gene expression regulation ; Genes ; Genetics & genetic processes ; Génétique & processus génétiques ; Heart ; HEK293 Cells ; HIV 1 ; Humans ; hypertrophy ; inflammation ; Life Sciences ; Mice ; Myosin Heavy Chains - genetics ; Myosin Heavy Chains - metabolism ; Myosin Heavy Chains/genetics/metabolism ; neoplasms ; Neurons and Cognition ; nucleoproteins ; Pathology ; Positive Transcriptional Elongation Factor B - genetics ; Positive Transcriptional Elongation Factor B - metabolism ; Positive Transcriptional Elongation Factor B/genetics/metabolism ; Promoter Regions, Genetic ; Protein Structure, Secondary ; Proteins ; repressor proteins ; Repressor Proteins - genetics ; Repressor Proteins - metabolism ; Repressor Proteins/genetics/metabolism ; Ribonucleic acid ; RNA ; RNA, Small Nuclear - genetics ; RNA, Small Nuclear - metabolism ; RNA, Small Nuclear/genetics/metabolism ; RNA-Binding Proteins - genetics ; RNA-Binding Proteins - metabolism ; RNA-Binding Proteins/genetics/metabolism ; Sciences du vivant ; Small nuclear RNA ; T lymphocytes ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Transcription Factors/genetics/metabolism ; Tumor Suppressor Proteins - genetics ; Tumor Suppressor Proteins - metabolism ; Tumor Suppressor Proteins/genetics/metabolism</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2013-07, Vol.110 (31), p.12655-12660</ispartof><rights>copyright © 1993-2008 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Jul 30, 2013</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c669t-85201f26ed9110256e25b0713485600c6c77ddbf945fbdfb65e104925e75de033</citedby><cites>FETCH-LOGICAL-c669t-85201f26ed9110256e25b0713485600c6c77ddbf945fbdfb65e104925e75de033</cites><orcidid>0000-0003-1234-7477 ; 0000-0003-4336-3437 ; 0000-0003-1647-8917 ; 0000-0002-6779-092X ; 0000-0002-0928-2185 ; 0000-0002-7121-823X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/110/31.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/42712662$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/42712662$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23852730$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-01544149$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Cherrier, Thomas</creatorcontrib><creatorcontrib>Le Douce, Valentin</creatorcontrib><creatorcontrib>Eilebrecht, Sebastian</creatorcontrib><creatorcontrib>Riclet, Raphael</creatorcontrib><creatorcontrib>Marban, Céline</creatorcontrib><creatorcontrib>Dequiedt, Franck</creatorcontrib><creatorcontrib>Goumon, Yannick</creatorcontrib><creatorcontrib>Paillart, Jean-Christophe</creatorcontrib><creatorcontrib>Mericskay, Mathias</creatorcontrib><creatorcontrib>Parlakian, Ara</creatorcontrib><creatorcontrib>Bausero, Pedro</creatorcontrib><creatorcontrib>Abbas, Wasim</creatorcontrib><creatorcontrib>Herbein, Georges</creatorcontrib><creatorcontrib>Kurdistani, Siavash K.</creatorcontrib><creatorcontrib>Grana, Xavier</creatorcontrib><creatorcontrib>Van Driessche, Benoit</creatorcontrib><creatorcontrib>Schwartz, Christian</creatorcontrib><creatorcontrib>Candolfi, Ermanno</creatorcontrib><creatorcontrib>Benecke, Arndt G.</creatorcontrib><creatorcontrib>Van Lint, Carine</creatorcontrib><creatorcontrib>Rohr, Olivier</creatorcontrib><title>CTIP2 is a negative regulator of P-TEFb</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The positive transcription elongation factor b (P-TEFb) is involved in physiological and pathological events including inflammation, cancer, AIDS, and cardiac hypertrophy. The balance between its active and inactive form is tightly controlled to ensure cellular integrity. We report that the transcriptional repressor CTIP2 is a major modulator of P-TEFb activity. CTIP2 copurifies and interacts with an inactive P-TEFb complex containing the 7SK snRNA and HEXIM1. CTIP2 associates directly with HEXIM1 and, via the loop 2 of the 7SK snRNA, with P-TEFb. In this nucleoprotein complex, CTIP2 significantly represses the Cdk9 kinase activity of P-TEFb. Accordingly, we show that CTIP2 inhibits large sets of P-TEFb- and 7SK snRNA-sensitive genes. In hearts of hypertrophic cardiomyopathic mice, CTIP2 controls P-TEFb-sensitive pathways involved in the establishment of this pathology. Overexpression of the β-myosin heavy chain protein contributes to the pathological cardiac wall thickening. The inactive P-TEFb complex associates with CTIP2 at the MYH7 gene promoter to repress its activity. Taken together, our results strongly suggest that CTIP2 controls P-TEFb function in physiological and pathological conditions.</description><subject>Acquired immune deficiency syndrome</subject><subject>AIDS</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Biochemistry, biophysics & molecular biology</subject><subject>Biochimie, biophysique & biologie moléculaire</subject><subject>Biological Sciences</subject><subject>Cancer</subject><subject>Cardiac Myosins - genetics</subject><subject>Cardiac Myosins - metabolism</subject><subject>Cardiac Myosins/genetics/metabolism</subject><subject>Cardiomegaly - genetics</subject><subject>Cardiomegaly - metabolism</subject><subject>Cardiomegaly - pathology</subject><subject>Cardiomegaly/genetics/metabolism/pathology</subject><subject>Cell lines</subject><subject>Cyclin-Dependent Kinase 9 - genetics</subject><subject>Cyclin-Dependent Kinase 9 - metabolism</subject><subject>Cyclin-Dependent Kinase 9/genetics/metabolism</subject><subject>Gene expression regulation</subject><subject>Genes</subject><subject>Genetics & genetic processes</subject><subject>Génétique & processus génétiques</subject><subject>Heart</subject><subject>HEK293 Cells</subject><subject>HIV 1</subject><subject>Humans</subject><subject>hypertrophy</subject><subject>inflammation</subject><subject>Life Sciences</subject><subject>Mice</subject><subject>Myosin Heavy Chains - genetics</subject><subject>Myosin Heavy Chains - metabolism</subject><subject>Myosin Heavy Chains/genetics/metabolism</subject><subject>neoplasms</subject><subject>Neurons and Cognition</subject><subject>nucleoproteins</subject><subject>Pathology</subject><subject>Positive Transcriptional Elongation Factor B - genetics</subject><subject>Positive Transcriptional Elongation Factor B - metabolism</subject><subject>Positive Transcriptional Elongation Factor B/genetics/metabolism</subject><subject>Promoter Regions, Genetic</subject><subject>Protein Structure, Secondary</subject><subject>Proteins</subject><subject>repressor proteins</subject><subject>Repressor Proteins - genetics</subject><subject>Repressor Proteins - metabolism</subject><subject>Repressor Proteins/genetics/metabolism</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Small Nuclear - genetics</subject><subject>RNA, Small Nuclear - metabolism</subject><subject>RNA, Small Nuclear/genetics/metabolism</subject><subject>RNA-Binding Proteins - genetics</subject><subject>RNA-Binding Proteins - metabolism</subject><subject>RNA-Binding Proteins/genetics/metabolism</subject><subject>Sciences du vivant</subject><subject>Small nuclear RNA</subject><subject>T lymphocytes</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Transcription Factors/genetics/metabolism</subject><subject>Tumor Suppressor Proteins - genetics</subject><subject>Tumor Suppressor Proteins - metabolism</subject><subject>Tumor Suppressor Proteins/genetics/metabolism</subject><issn>0027-8424</issn><issn>1091-6490</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks1v1DAQxS0EokvhzAmIxAE4pJ3xZ3xBqlYtrbQSldieLSdx0qyyydZOVuK_x2mWBXrhZMvze29G40fIW4QzBMXOd50NZ0gpIJOI8IwsEDSmkmt4ThYAVKUZp_yEvAphAwBaZPCSnFCWCaoYLMin5frmliZNSGzSudoOzd4l3tVja4feJ32V3Kbry6v8NXlR2Ta4N4fzlNxdXa6X1-nq-7eb5cUqLaTUQxptASsqXanjOFRIR0UOChnPhAQoZKFUWeaV5qLKyyqXwiFwTYVTonTA2Cn5OvvuxnzrysJ1g7et2flma_1P09vG_FvpmntT93vDFKNaQzRgs0HbuNqZ3ueN2dNH4eN9bGtjC5M7Q6nMDEqOqKPqy6y6f9Ls-mJlpjdAwTlyvcfIfj6M6PuH0YXBbJtQuLa1nevHYDADhgwV5_9HOca1Cc1lRD8-QTf96Lu464nKqNScikidz1Th-xC8q47DIpgpEWZKhPmTiKh4__dCj_zvCEQgOQCT8mgX_RhGIymmru9mZBNiKI4MpyrWJY31D3O9sr2xtW-CufsRJ4g_jkxlmLFfu2XI9A</recordid><startdate>20130730</startdate><enddate>20130730</enddate><creator>Cherrier, Thomas</creator><creator>Le Douce, Valentin</creator><creator>Eilebrecht, Sebastian</creator><creator>Riclet, Raphael</creator><creator>Marban, Céline</creator><creator>Dequiedt, Franck</creator><creator>Goumon, Yannick</creator><creator>Paillart, Jean-Christophe</creator><creator>Mericskay, Mathias</creator><creator>Parlakian, Ara</creator><creator>Bausero, Pedro</creator><creator>Abbas, Wasim</creator><creator>Herbein, Georges</creator><creator>Kurdistani, Siavash K.</creator><creator>Grana, Xavier</creator><creator>Van Driessche, Benoit</creator><creator>Schwartz, Christian</creator><creator>Candolfi, Ermanno</creator><creator>Benecke, Arndt G.</creator><creator>Van Lint, Carine</creator><creator>Rohr, Olivier</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>1XC</scope><scope>Q33</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1234-7477</orcidid><orcidid>https://orcid.org/0000-0003-4336-3437</orcidid><orcidid>https://orcid.org/0000-0003-1647-8917</orcidid><orcidid>https://orcid.org/0000-0002-6779-092X</orcidid><orcidid>https://orcid.org/0000-0002-0928-2185</orcidid><orcidid>https://orcid.org/0000-0002-7121-823X</orcidid></search><sort><creationdate>20130730</creationdate><title>CTIP2 is a negative regulator of P-TEFb</title><author>Cherrier, Thomas ; Le Douce, Valentin ; Eilebrecht, Sebastian ; Riclet, Raphael ; Marban, Céline ; Dequiedt, Franck ; Goumon, Yannick ; Paillart, Jean-Christophe ; Mericskay, Mathias ; Parlakian, Ara ; Bausero, Pedro ; Abbas, Wasim ; Herbein, Georges ; Kurdistani, Siavash K. ; Grana, Xavier ; Van Driessche, Benoit ; Schwartz, Christian ; Candolfi, Ermanno ; Benecke, Arndt G. ; Van Lint, Carine ; Rohr, Olivier</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c669t-85201f26ed9110256e25b0713485600c6c77ddbf945fbdfb65e104925e75de033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acquired immune deficiency syndrome</topic><topic>AIDS</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Biochemistry, biophysics & molecular biology</topic><topic>Biochimie, biophysique & biologie moléculaire</topic><topic>Biological Sciences</topic><topic>Cancer</topic><topic>Cardiac Myosins - genetics</topic><topic>Cardiac Myosins - metabolism</topic><topic>Cardiac Myosins/genetics/metabolism</topic><topic>Cardiomegaly - genetics</topic><topic>Cardiomegaly - metabolism</topic><topic>Cardiomegaly - pathology</topic><topic>Cardiomegaly/genetics/metabolism/pathology</topic><topic>Cell lines</topic><topic>Cyclin-Dependent Kinase 9 - genetics</topic><topic>Cyclin-Dependent Kinase 9 - metabolism</topic><topic>Cyclin-Dependent Kinase 9/genetics/metabolism</topic><topic>Gene expression regulation</topic><topic>Genes</topic><topic>Genetics & genetic processes</topic><topic>Génétique & processus génétiques</topic><topic>Heart</topic><topic>HEK293 Cells</topic><topic>HIV 1</topic><topic>Humans</topic><topic>hypertrophy</topic><topic>inflammation</topic><topic>Life Sciences</topic><topic>Mice</topic><topic>Myosin Heavy Chains - genetics</topic><topic>Myosin Heavy Chains - metabolism</topic><topic>Myosin Heavy Chains/genetics/metabolism</topic><topic>neoplasms</topic><topic>Neurons and Cognition</topic><topic>nucleoproteins</topic><topic>Pathology</topic><topic>Positive Transcriptional Elongation Factor B - genetics</topic><topic>Positive Transcriptional Elongation Factor B - metabolism</topic><topic>Positive Transcriptional Elongation Factor B/genetics/metabolism</topic><topic>Promoter Regions, Genetic</topic><topic>Protein Structure, Secondary</topic><topic>Proteins</topic><topic>repressor proteins</topic><topic>Repressor Proteins - genetics</topic><topic>Repressor Proteins - metabolism</topic><topic>Repressor Proteins/genetics/metabolism</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA, Small Nuclear - genetics</topic><topic>RNA, Small Nuclear - metabolism</topic><topic>RNA, Small Nuclear/genetics/metabolism</topic><topic>RNA-Binding Proteins - genetics</topic><topic>RNA-Binding Proteins - metabolism</topic><topic>RNA-Binding Proteins/genetics/metabolism</topic><topic>Sciences du vivant</topic><topic>Small nuclear RNA</topic><topic>T lymphocytes</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Transcription Factors/genetics/metabolism</topic><topic>Tumor Suppressor Proteins - genetics</topic><topic>Tumor Suppressor Proteins - metabolism</topic><topic>Tumor Suppressor Proteins/genetics/metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cherrier, Thomas</creatorcontrib><creatorcontrib>Le Douce, Valentin</creatorcontrib><creatorcontrib>Eilebrecht, Sebastian</creatorcontrib><creatorcontrib>Riclet, Raphael</creatorcontrib><creatorcontrib>Marban, Céline</creatorcontrib><creatorcontrib>Dequiedt, Franck</creatorcontrib><creatorcontrib>Goumon, Yannick</creatorcontrib><creatorcontrib>Paillart, Jean-Christophe</creatorcontrib><creatorcontrib>Mericskay, Mathias</creatorcontrib><creatorcontrib>Parlakian, Ara</creatorcontrib><creatorcontrib>Bausero, Pedro</creatorcontrib><creatorcontrib>Abbas, Wasim</creatorcontrib><creatorcontrib>Herbein, Georges</creatorcontrib><creatorcontrib>Kurdistani, Siavash K.</creatorcontrib><creatorcontrib>Grana, Xavier</creatorcontrib><creatorcontrib>Van Driessche, Benoit</creatorcontrib><creatorcontrib>Schwartz, Christian</creatorcontrib><creatorcontrib>Candolfi, Ermanno</creatorcontrib><creatorcontrib>Benecke, Arndt G.</creatorcontrib><creatorcontrib>Van Lint, Carine</creatorcontrib><creatorcontrib>Rohr, Olivier</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Université de Liège - Open Repository and Bibliography (ORBI)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cherrier, Thomas</au><au>Le Douce, Valentin</au><au>Eilebrecht, Sebastian</au><au>Riclet, Raphael</au><au>Marban, Céline</au><au>Dequiedt, Franck</au><au>Goumon, Yannick</au><au>Paillart, Jean-Christophe</au><au>Mericskay, Mathias</au><au>Parlakian, Ara</au><au>Bausero, Pedro</au><au>Abbas, Wasim</au><au>Herbein, Georges</au><au>Kurdistani, Siavash K.</au><au>Grana, Xavier</au><au>Van Driessche, Benoit</au><au>Schwartz, Christian</au><au>Candolfi, Ermanno</au><au>Benecke, Arndt G.</au><au>Van Lint, Carine</au><au>Rohr, Olivier</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CTIP2 is a negative regulator of P-TEFb</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2013-07-30</date><risdate>2013</risdate><volume>110</volume><issue>31</issue><spage>12655</spage><epage>12660</epage><pages>12655-12660</pages><issn>0027-8424</issn><issn>1091-6490</issn><eissn>1091-6490</eissn><abstract>The positive transcription elongation factor b (P-TEFb) is involved in physiological and pathological events including inflammation, cancer, AIDS, and cardiac hypertrophy. The balance between its active and inactive form is tightly controlled to ensure cellular integrity. We report that the transcriptional repressor CTIP2 is a major modulator of P-TEFb activity. CTIP2 copurifies and interacts with an inactive P-TEFb complex containing the 7SK snRNA and HEXIM1. CTIP2 associates directly with HEXIM1 and, via the loop 2 of the 7SK snRNA, with P-TEFb. In this nucleoprotein complex, CTIP2 significantly represses the Cdk9 kinase activity of P-TEFb. Accordingly, we show that CTIP2 inhibits large sets of P-TEFb- and 7SK snRNA-sensitive genes. In hearts of hypertrophic cardiomyopathic mice, CTIP2 controls P-TEFb-sensitive pathways involved in the establishment of this pathology. Overexpression of the β-myosin heavy chain protein contributes to the pathological cardiac wall thickening. The inactive P-TEFb complex associates with CTIP2 at the MYH7 gene promoter to repress its activity. Taken together, our results strongly suggest that CTIP2 controls P-TEFb function in physiological and pathological conditions.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>23852730</pmid><doi>10.1073/pnas.1220136110</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0003-1234-7477</orcidid><orcidid>https://orcid.org/0000-0003-4336-3437</orcidid><orcidid>https://orcid.org/0000-0003-1647-8917</orcidid><orcidid>https://orcid.org/0000-0002-6779-092X</orcidid><orcidid>https://orcid.org/0000-0002-0928-2185</orcidid><orcidid>https://orcid.org/0000-0002-7121-823X</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0027-8424 |
ispartof | Proceedings of the National Academy of Sciences - PNAS, 2013-07, Vol.110 (31), p.12655-12660 |
issn | 0027-8424 1091-6490 1091-6490 |
language | eng |
recordid | cdi_pubmed_primary_23852730 |
source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
subjects | Acquired immune deficiency syndrome AIDS Animals Antibodies Biochemistry, biophysics & molecular biology Biochimie, biophysique & biologie moléculaire Biological Sciences Cancer Cardiac Myosins - genetics Cardiac Myosins - metabolism Cardiac Myosins/genetics/metabolism Cardiomegaly - genetics Cardiomegaly - metabolism Cardiomegaly - pathology Cardiomegaly/genetics/metabolism/pathology Cell lines Cyclin-Dependent Kinase 9 - genetics Cyclin-Dependent Kinase 9 - metabolism Cyclin-Dependent Kinase 9/genetics/metabolism Gene expression regulation Genes Genetics & genetic processes Génétique & processus génétiques Heart HEK293 Cells HIV 1 Humans hypertrophy inflammation Life Sciences Mice Myosin Heavy Chains - genetics Myosin Heavy Chains - metabolism Myosin Heavy Chains/genetics/metabolism neoplasms Neurons and Cognition nucleoproteins Pathology Positive Transcriptional Elongation Factor B - genetics Positive Transcriptional Elongation Factor B - metabolism Positive Transcriptional Elongation Factor B/genetics/metabolism Promoter Regions, Genetic Protein Structure, Secondary Proteins repressor proteins Repressor Proteins - genetics Repressor Proteins - metabolism Repressor Proteins/genetics/metabolism Ribonucleic acid RNA RNA, Small Nuclear - genetics RNA, Small Nuclear - metabolism RNA, Small Nuclear/genetics/metabolism RNA-Binding Proteins - genetics RNA-Binding Proteins - metabolism RNA-Binding Proteins/genetics/metabolism Sciences du vivant Small nuclear RNA T lymphocytes Transcription Factors - genetics Transcription Factors - metabolism Transcription Factors/genetics/metabolism Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - metabolism Tumor Suppressor Proteins/genetics/metabolism |
title | CTIP2 is a negative regulator of P-TEFb |
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