Lookup NU author(s): Dr Sonja Baumli,
Dr Alison Hole,
Professor Martin Noble,
Professor Jane Endicott
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CDK9, the kinase of positive transcription elongation factor b (P-TEFb), stimulates transcription elongation by phosphorylating RNA polymerase II and transcription elongation factors. Using kinetic analysis of a human P-TEFb complex consisting of CDK9 and cyclin T, we show that the CDK9 C-terminal tail sequence is important for the catalytic mechanism and imposes an ordered binding of substrates and release of products. Crystallographic analysis of a CDK9/cyclin T complex in which the C-terminal tail partially blocks the ATP binding site reveals a possible reaction intermediate. Biochemical characterization of CDK9 mutants supports a model in which the CDK9 tail cycles through different conformational states. We propose that this mechanism is critical for the pattern of CTD Ser2 phosphorylation on actively transcribed genes.
Author(s): Baumli S, Hole AJ, Wang LZ, Noble MEM, Endicott JA
Publication type: Article
Publication status: Published
Print publication date: 10/10/2012
ISSN (print): 0969-2126
ISSN (electronic): 1878-4186
Publisher: Cell Press
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