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PMID: 18513937 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

The multi-tasking P-TEFb complex.

Current opinion in cell biology ·Vol. 20 ·No. 3 ·2008-06-00 ·Pages 334-40

Brès V, Yoh SM, Jones KA

Abstract

P-TEFb (CycT1:Cdk9), the metazoan RNA polymerase II Ser2 C-terminal domain (CTD) kinase, regulates transcription elongation at many genes and integrates mRNA synthesis with histone modification, pre-mRNA processing, and mRNA export. Recruitment of P-TEFb to target genes requires deubiquitination of H2Bub, phosphorylation of H3S10, and the bromodomain protein, Brd4. Brd4 activates growth-related genes in the G1 phase of the cell cycle and can also tether P-TEFb to mitotic chromosomes, possibly to mark sites of active transcription throughout cell division. P-TEFb co-operates with c-Myc during transactivation and cell transformation, and also requires SKIP (c-Ski-interacting protein), an mRNA elongation and splicing factor. Some functions of the P-TEFb/Ser2P CTD are executed by the Spt6 transcription elongation factor, which binds directly to the phosphorylated CTD and recruits the Iws1 ('interacts with Spt6') protein. Iws1, in turn, interacts with the REF1/Aly nuclear export adaptor and stimulates the kinetics of mRNA export. Given the prominent role of Spt6 in regulating chromatin structure, the CTD-bound Spt6:Iws1 complex may also control histone modifications during elongation. Following transcription, P-TEFb accompanies the mature mRNA to the cytoplasm to promote translation elongation.

MeSH Terms
Animals Cell Cycle Proteins Histones/genetics,metabolism Humans Methylation Nuclear Proteins/genetics,metabolism Phosphoric Monoester Hydrolases/genetics,metabolism Positive Transcriptional Elongation Factor B/genetics,metabolism Protein Biosynthesis/genetics RNA, Messenger/biosynthesis,genetics Transcription Factors/genetics,metabolism Transcription, Genetic/genetics
Chemicals
BRD4 protein, human Cell Cycle Proteins Histones Nuclear Proteins RNA, Messenger SUPT6H protein, human Transcription Factors Positive Transcriptional Elongation Factor B SKIP enzyme, human Phosphoric Monoester Hydrolases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Brès Vanessa
Regulatory Biology Laboratory, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037-1099, USA.
Yoh Sunnie M
Jones Katherine A
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Article Info
Journal
Current opinion in cell biology
Abbr.
Curr Opin Cell Biol
ISSN
0955-0674
DOI
10.1016/j.ceb.2008.04.008
Published
2008-06-00
Epub
2008-00-29
Pages
334-40
Language
English
Region
England
NLM ID
8913428
PMCID
PMC2628440
Subset
IM
Grants
NCI NIH HHS · CA125535 · United States
NCI NIH HHS · R01 CA125535 · United States
NIAID NIH HHS · AI044615 · United States
NCI NIH HHS · P01 CA054418 · United States
NIAID NIH HHS · R56 AI044615 · United States
NCI NIH HHS · P01 CA054418-120011 · United States
NIAID NIH HHS · R01 AI044615-10 · United States
NIAID NIH HHS · R01 AI044615 · United States
External Links
PubMed source DOI: 10.1016/j.ceb.2008.04.008 PMC Full Text View journal details
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