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Phosphorylated Positive Transcription Elongation Factor b (P-TEFb) Is Tagged for Inhibition through Association with 7SK snRNA.
- Source :
-
Journal of Biological Chemistry . 2/6/2004, Vol. 279 Issue 6, p4153-4160. 8p. 17 Black and White Photographs, 5 Diagrams. - Publication Year :
- 2004
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Abstract
- The positive transcription elongation factor b (PTEFb), comprising CDK9 and cyclin T, stimulates transcription of cellular and viral genes by phosphorylating RNA polymerase II. A major portion of nuclear P-TEFb is sequestered and inactivated by the coordinated actions of the 7SK snRNA and the HEXIM1 protein, whose induced dissociation from P-TEFb is crucial for stressinduced transcription and pathogenesis of cardiac hypertrophy. The 7SK·P-TEFb interaction, which can occur independently of HEXIM1 and does not by itself inhibit P-TEFb, recruits HEXIM1 for P-TEFb inactivation. To study the control of this interaction, we established an in vitro system that reconstituted the specific interaction of P-TEFb with 7SK but not other snRNAs. Using this system, together with an in vivo binding assay, we show that the phosphorylation of CDK9, on possibly the conserved Thr-186 in the T-loop, was crucial for the 7SK·P-TEFb interaction. This phosphorylation was not caused by CDK9 autophosphorylation or the general CDK-activating kinase CAK, but rather by a novel HeLa nuclear kinase. Furthermore, the stress-induced disruption of the 7SK·P-TEFb interaction was not caused by any prohibitive changes in 7SK but by the dephosphorylation of P-TEFb, leading to the loss of the key phosphorylation important for 7SK binding. Thus, the phosphorylated P-TEFb is tagged for inhibition through association with 7SK. We discuss the implications of this mechanism in controlling P-TEFb activity during normal and stress-induced transcription. [ABSTRACT FROM AUTHOR]
- Subjects :
- *TRANSCRIPTION factors
*CYCLINS
*VIRAL genetics
*BIOCHEMISTRY
*BIOLOGY
*CHEMISTRY
Subjects
Details
- Language :
- English
- ISSN :
- 00219258
- Volume :
- 279
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 12507262
- Full Text :
- https://doi.org/10.1074/jbc.M310044200