Human Cyclin Dependent Kinase 9, CDK9 ELI

Protein kinase involved in the regulation of transcription (PubMed: 10574912, PubMed: 10757782, PubMed: 11145967, PubMed: 11575923, PubMed: 11809800, PubMed: 11884399, PubMed: 14701750, PubMed: 16109376, PubMed: 16109377, PubMed: 20930849, PubMed: 28426094).

Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A, SUPT5H and RDBP (PubMed: 10574912, PubMed: 10757782, PubMed: 11145967, PubMed: 11575923, PubMed: 11809800, PubMed: 11884399, PubMed: 14701750, PubMed: 16109376, PubMed: 16109377, PubMed: 20930849, PubMed: 28426094).

This complex is inactive when in the 7SK snRNP complex form (PubMed: 10574912, PubMed: 10757782, PubMed: 11145967, PubMed: 11575923, PubMed: 11809800, PubMed: 11884399, PubMed: 14701750, PubMed: 16109376, PubMed: 16109377, PubMed: 20930849, PubMed: 28426094).

Phosphorylates EP300, MYOD1, RPB1/POLR2A and AR and the negative elongation factors DSIF and NELF (PubMed: 9857195, PubMed: 10912001, PubMed: 11112772, PubMed: 12037670, PubMed: 20081228, PubMed: 20980437, PubMed: 21127351).

Regulates cytokine inducible transcription networks by facilitating promoter recognition of target transcription factors (e.g.

TNF-inducible RELA/p65 activation and IL-6-inducible STAT3 signaling) (PubMed: 17956865, PubMed: 18362169).

Promotes RNA synthesis in genetic programs for cell growth, differentiation and viral pathogenesis (PubMed: 10393184, PubMed: 11112772).

P-TEFb is also involved in cotranscriptional histone modification, mRNA processing and mRNA export (PubMed: 15564463, PubMed: 19575011, PubMed: 19844166).

Modulates a complex network of chromatin modifications including histone H2B monoubiquitination (H2Bub1), H3 lysine 4 trimethylation (H3K4me3) and H3K36me3; integrates phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing (PubMed: 15564463, PubMed: 19575011, PubMed: 19844166).

The CDK9/cyclin-K complex has also a kinase activity towards CTD of RNAP II and can substitute for CDK9/cyclin-T P-TEFb in vitro (PubMed: 21127351).

Replication stress response protein; the CDK9/cyclin-K complex is required for genome integrity maintenance, by promoting cell cycle recovery from replication arrest and limiting single-stranded DNA amount in response to replication stress, thus reducing the breakdown of stalled replication forks and avoiding DNA damage (PubMed: 20493174).

In addition, probable function in DNA repair of isoform 2 via interaction with KU70/XRCC6 (PubMed: 20493174).

Promotes cardiac myocyte enlargement (PubMed: 20081228).

RPB1/POLR2A phosphorylation on 'Ser-2' in CTD activates transcription (PubMed: 21127351).

AR phosphorylation modulates AR transcription factor promoter selectivity and cell growth.

DSIF and NELF phosphorylation promotes transcription by inhibiting their negative effect (PubMed: 9857195, PubMed: 10912001, PubMed: 11112772).

The phosphorylation of MYOD1 enhances its transcriptional activity and thus promotes muscle differentiation (PubMed: 12037670).