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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2013-07, Vol.110 (31), p.12655-12660
Hauptverfasser: 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
Format: Artikel
Sprache:eng
Schlagworte:
RNA
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 12660
container_issue 31
container_start_page 12655
container_title Proceedings of the National Academy of Sciences - PNAS
container_volume 110
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
fullrecord <record><control><sourceid>jstor_pubme</sourceid><recordid>TN_cdi_pubmed_primary_23852730</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>42712662</jstor_id><sourcerecordid>42712662</sourcerecordid><originalsourceid>FETCH-LOGICAL-c669t-85201f26ed9110256e25b0713485600c6c77ddbf945fbdfb65e104925e75de033</originalsourceid><addsrcrecordid>eNqFks1v1DAQxS0EokvhzAmIxAE4pJ3xZ3xBqlYtrbQSldieLSdx0qyyydZOVuK_x2mWBXrhZMvze29G40fIW4QzBMXOd50NZ0gpIJOI8IwsEDSmkmt4ThYAVKUZp_yEvAphAwBaZPCSnFCWCaoYLMin5frmliZNSGzSudoOzd4l3tVja4feJ32V3Kbry6v8NXlR2Ta4N4fzlNxdXa6X1-nq-7eb5cUqLaTUQxptASsqXanjOFRIR0UOChnPhAQoZKFUWeaV5qLKyyqXwiFwTYVTonTA2Cn5OvvuxnzrysJ1g7et2flma_1P09vG_FvpmntT93vDFKNaQzRgs0HbuNqZ3ueN2dNH4eN9bGtjC5M7Q6nMDEqOqKPqy6y6f9Ls-mJlpjdAwTlyvcfIfj6M6PuH0YXBbJtQuLa1nevHYDADhgwV5_9HOca1Cc1lRD8-QTf96Lu464nKqNScikidz1Th-xC8q47DIpgpEWZKhPmTiKh4__dCj_zvCEQgOQCT8mgX_RhGIymmru9mZBNiKI4MpyrWJY31D3O9sr2xtW-CufsRJ4g_jkxlmLFfu2XI9A</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1418269425</pqid></control><display><type>article</type><title>CTIP2 is a negative regulator of P-TEFb</title><source>Jstor Complete Legacy</source><source>MEDLINE</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><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</creator><creatorcontrib>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</creatorcontrib><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><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 &amp; molecular biology ; Biochimie, biophysique &amp; 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 &amp; genetic processes ; Génétique &amp; 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 &amp; molecular biology</subject><subject>Biochimie, biophysique &amp; 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 &amp; genetic processes</subject><subject>Génétique &amp; 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 &amp; molecular biology</topic><topic>Biochimie, biophysique &amp; 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 &amp; genetic processes</topic><topic>Génétique &amp; 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 &amp; 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
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T16%3A13%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=CTIP2%20is%20a%20negative%20regulator%20of%20P-TEFb&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Cherrier,%20Thomas&rft.date=2013-07-30&rft.volume=110&rft.issue=31&rft.spage=12655&rft.epage=12660&rft.pages=12655-12660&rft.issn=0027-8424&rft.eissn=1091-6490&rft_id=info:doi/10.1073/pnas.1220136110&rft_dat=%3Cjstor_pubme%3E42712662%3C/jstor_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1418269425&rft_id=info:pmid/23852730&rft_jstor_id=42712662&rfr_iscdi=true