Transcription Factor IIS Cooperates with the E3 Ligase UBR5 to Ubiquitinate the CDK9 Subunit of the Positive Transcription Elongation Factor B

Marilena Cojocaru; Annie Bouchard; Philippe Cloutier; Jeff J Cooper; Katayoun Varzavand; David H Price; Benoit Coulombe

doi:10.1074/jbc.M110.176628

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Transcription Factor IIS Cooperates with the E3 Ligase UBR5 to Ubiquitinate the CDK9 Subunit of the Positive Transcription Elongation Factor B

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Transcription Factor IIS Cooperates with the E3 Ligase UBR5 to Ubiquitinate the CDK9 Subunit of the Positive Transcription Elongation Factor B

Marilena Cojocaru, Annie Bouchard, Philippe Cloutier, Jeff J Cooper, Katayoun Varzavand, David H Price and Benoit Coulombe

The Journal of biological chemistry, Vol.286(7), pp.5012-5022

02/18/2011

DOI: 10.1074/jbc.M110.176628

PMCID: PMC3037613

PMID: 21127351

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Abstract

Elongation of transcription by mammalian RNA polymerase II (RNAPII) is regulated by specific factors, including transcription factor IIS (TFIIS) and positive transcription elongation factor b (P-TEFb). We show that the E3 ubiquitin ligase UBR5 associates with the CDK9 subunit of positive transcription elongation factor b to mediate its polyubiquitination in human cells. TFIIS also binds UBR5 to stimulate CDK9 polyubiquitination. Co-localization of UBR5, CDK9, and TFIIS along specific regions of the γ fibrinogen (γFBG) gene indicates that a ternary complex involving these factors participates in the transcriptional regulation of this gene. In support of this notion, overexpression of TFIIS not only modifies the ubiquitination pattern of CDK9 in vivo but also increases the association of CDK9 with various regions of the γFBG gene. Notably, the TFIIS-mediated increase in CDK9 loading is obtained during both basal and activated transcription of the γFBG gene. This increased CDK9 binding is paralleled by an increase in the recruitment of RNAPII along the γFBG gene and the phosphorylation of the C-terminal domain of the RNAPII largest subunit RPB1 on Ser-2, a known target of CDK9. Together, these results identify UBR5 as a novel E3 ligase that regulates transcription and define an additional function of TFIIS in the regulation of CDK9.

Gene Regulation

Transcription Regulation

Ubiquitin Ligase

RNA Polymerase II

Protein-Protein Interactions

Transcription Elongation Factors

Details

Title: Subtitle: Transcription Factor IIS Cooperates with the E3 Ligase UBR5 to Ubiquitinate the CDK9 Subunit of the Positive Transcription Elongation Factor B
Creators: Marilena Cojocaru - From the
Annie Bouchard - From the
Philippe Cloutier - From the
Jeff J Cooper - the
Katayoun Varzavand - the
David H Price - the
Benoit Coulombe - From the
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.286(7), pp.5012-5022
DOI: 10.1074/jbc.M110.176628
PMID: 21127351
PMCID: PMC3037613
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: American Society for Biochemistry and Molecular Biology; 9650 Rockville Pike, Bethesda, MD 20814, U.S.A
Alternative title: Ubiquitination of CDK9 by the E3 Ligase UBR5
Language: English
Date published: 02/18/2011
Academic Unit: The University of Iowa Institute for Vision Research; Biochemistry and Molecular Biology
Record Identifier: 9984024420002771

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