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The CDK9 tail determines the reaction pathway of positive transcription elongation factor b.

ABSTRACT: 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.

SUBMITTER: Baumli S

PROVIDER: S-EPMC3469819 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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The CDK9 tail determines the reaction pathway of positive transcription elongation factor b.

Baumli Sonja S Hole Alison J AJ Wang Lan-Zhen LZ Noble Martin E M ME Endicott Jane A JA

Structure (London, England : 1993) 20120906 10

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 ...[more]

PMID: 22959624

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