Catalytic activity of Cdk9 is required for nuclear co-localization of the Cdk9/cyclin T1 (P-TEFb) complex
- PMID: 12942536
- DOI: 10.1002/jcp.10376
Catalytic activity of Cdk9 is required for nuclear co-localization of the Cdk9/cyclin T1 (P-TEFb) complex
Abstract
Cdk9 and its binding partner cyclin T1 comprise the positive elongation factor b (P-TEFb). P-TEFb phosphorylates the RNA polymerase II carboxyl-terminal-domain (CTD) allowing efficient transcription elongation. Recent studies showed that Cdk9 is a predominant nuclear protein, and here we investigated the functional requirement for nuclear localization of Cdk9. We found that the catalytic inactive kinase mutant (Cdk9dn) fails to accumulate in the nucleus showing a diffuse sub-cellular localization. In addition to the catalityc activity, nuclear localization of Cdk9 protein requires the presence of the phospho-acceptor sites at the C-terminus tail. Finally, enforced expression of wild-type cyclinT1, which enhances nuclear localization of Cdk9wt, fails to direct the Cdk9 mutants to the nucleus. Collectively, these findings implicate that nuclear localization of Cdk9 requires auto-phosphorylation of the kinase, and highlight the presence of a regulatory mechanism underlying the nuclear localization of the P-TEFb complex.
Copyright 2003 Wiley-Liss, Inc.
Similar articles
-
CDK9 has the intrinsic property to shuttle between nucleus and cytoplasm, and enhanced expression of cyclin T1 promotes its nuclear localization.J Cell Physiol. 2002 Aug;192(2):209-15. doi: 10.1002/jcp.10130. J Cell Physiol. 2002. PMID: 12115727
-
T-loop phosphorylated Cdk9 localizes to nuclear speckle domains which may serve as sites of active P-TEFb function and exchange between the Brd4 and 7SK/HEXIM1 regulatory complexes.J Cell Physiol. 2010 Jul;224(1):84-93. doi: 10.1002/jcp.22096. J Cell Physiol. 2010. PMID: 20201073 Free PMC article.
-
Regulatory functions of Cdk9 and of cyclin T1 in HIV tat transactivation pathway gene expression.J Cell Biochem. 1999 Dec 1;75(3):357-68. J Cell Biochem. 1999. PMID: 10536359 Review.
-
Bromodomain protein Brd4 regulates human immunodeficiency virus transcription through phosphorylation of CDK9 at threonine 29.J Virol. 2009 Jan;83(2):1036-44. doi: 10.1128/JVI.01316-08. Epub 2008 Oct 29. J Virol. 2009. PMID: 18971272 Free PMC article.
-
Cellular control of gene expression by T-type cyclin/CDK9 complexes.Gene. 2004 Aug 4;337:15-23. doi: 10.1016/j.gene.2004.05.007. Gene. 2004. PMID: 15276198 Review.
Cited by
-
Functional characterization of a new member of the Cdk9 family in Aspergillus nidulans.Eukaryot Cell. 2010 Dec;9(12):1901-12. doi: 10.1128/EC.00384-09. Epub 2010 Oct 15. Eukaryot Cell. 2010. PMID: 20952582 Free PMC article.
-
The CDK9/cyclin T1 subunits of P-TEFb in mouse oocytes and preimplantation embryos: a possible role in embryonic genome activation.BMC Dev Biol. 2011 Jun 3;11:33. doi: 10.1186/1471-213X-11-33. BMC Dev Biol. 2011. PMID: 21639898 Free PMC article.
-
Function-guided proximity mapping unveils electrophilic-metabolite sensing by proteins not present in their canonical locales.Proc Natl Acad Sci U S A. 2022 Feb 1;119(5):e2120687119. doi: 10.1073/pnas.2120687119. Proc Natl Acad Sci U S A. 2022. PMID: 35082156 Free PMC article.
-
The structure of P-TEFb (CDK9/cyclin T1), its complex with flavopiridol and regulation by phosphorylation.EMBO J. 2008 Jul 9;27(13):1907-18. doi: 10.1038/emboj.2008.121. Epub 2008 Jun 19. EMBO J. 2008. PMID: 18566585 Free PMC article.
-
Regulation of P-TEFb elongation complex activity by CDK9 acetylation.Mol Cell Biol. 2007 Jul;27(13):4641-51. doi: 10.1128/MCB.00857-06. Epub 2007 Apr 23. Mol Cell Biol. 2007. PMID: 17452463 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous
