PKC phosphorylates HEXIM1 and regulates P-TEFb activity

Koh Fujinaga; Matjaz Barboric; Qintong Li; Zeping Luo; David H Price; B. Matija Peterlin

doi:10.1093/nar/gks682

Back

PKC phosphorylates HEXIM1 and regulates P-TEFb activity

Journal article

Open access

Peer reviewed

PKC phosphorylates HEXIM1 and regulates P-TEFb activity

Koh Fujinaga, Matjaz Barboric, Qintong Li, Zeping Luo, David H Price and B. Matija Peterlin

Nucleic acids research, Vol.40(18), pp.9160-9170

10/2012

DOI: 10.1093/nar/gks682

PMCID: PMC3467075

PMID: 22821562

Files and links (1)

url

https://doi.org/10.1093/nar/gks682View

Published (Version of record) Open Access

Abstract

The positive transcription elongation factor b (P-TEFb) regulates RNA polymerase II elongation. In cells, P-TEFb partitions between small active and larger inactive states. In the latter, HEXIM1 binds to 7SK snRNA and recruits as well as inactivates P-TEFb in the 7SK snRNP. Several stimuli can affect this P-TEFb equilibrium. In this study, we demonstrate that protein kinase C (PKC) phosphorylates the serine at position158 (S158) in HEXIM1. This phosphorylated HEXIM1 protein neither binds to 7SK snRNA nor inhibits P-TEFb. Phorbol esters or the engagement of the T cell antigen receptor, which activate PKC and the expression of the constitutively active (CA) PKCθ protein, which is found in T cells, inhibit the formation of the 7SK snRNP. All these stimuli increase P-TEFb-dependent transcription. In contrast, the kinase-negative PKCθ and the mutant HEXIM1 (S158A) proteins block effects of these PKC-activating stimuli. These results indicate that the phosphorylation of HEXIM1 by PKC represents a major regulatory step of P-TEFb activity in cells.

Molecular Biology

Details

Title: Subtitle: PKC phosphorylates HEXIM1 and regulates P-TEFb activity
Creators: Koh Fujinaga - Departments of Medicine, Microbiology and Immunology, Rosalind Russell Research Center, University of California, San Francisco, San Francisco, CA 94143-0703, USA
Matjaz Barboric - Departments of Medicine, Microbiology and Immunology, Rosalind Russell Research Center, University of California, San Francisco, San Francisco, CA 94143-0703, USA
Qintong Li - Departments of Medicine, Microbiology and Immunology, Rosalind Russell Research Center, University of California, San Francisco, San Francisco, CA 94143-0703, USA
Zeping Luo - Departments of Medicine, Microbiology and Immunology, Rosalind Russell Research Center, University of California, San Francisco, San Francisco, CA 94143-0703, USA
David H Price - Departments of Medicine, Microbiology and Immunology, Rosalind Russell Research Center, University of California, San Francisco, San Francisco, CA 94143-0703, USA
B. Matija Peterlin - Departments of Medicine, Microbiology and Immunology, Rosalind Russell Research Center, University of California, San Francisco, San Francisco, CA 94143-0703, USA
Resource Type: Journal article
Publication Details: Nucleic acids research, Vol.40(18), pp.9160-9170
DOI: 10.1093/nar/gks682
PMID: 22821562
PMCID: PMC3467075
NLM abbreviation: Nucleic Acids Res
ISSN: 0305-1048
eISSN: 1362-4962
Publisher: Oxford University Press
Language: English
Date published: 10/2012
Academic Unit: Biochemistry and Molecular Biology
Record Identifier: 9984024553002771

Metrics

17 Record Views

45 Times Cited - Web of Science