CDK8 (cyclin-dependent kinase 8)

GWB-BD17F8

1:12500

Component of the Mediator complex a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II) which may inhibit the formation of a transcription initiation complex. Phosphorylates CCNH leading to down-regulation of the TFIIH complex and transcriptional repression. Recruited through interaction with MAML1 to hyperphosphorylate the intracellular domain of NOTCH leading to its degradation.

ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate. Cofactor: Magnesium (By similarity).

Nucleus (Probable).

Contains 1 protein kinase domain. Summary: The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK family members are highly similar to the gene products of Saccharomyces cerevisiae cdc28 and Schizosaccharomyces pombe cdc2 and are known to be important regulators of cell cycle progression. This kinase and its regulatory subunit cyclin C are components of the RNA polymerase II holoenzyme complex which phosphorylates the carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II. This kinase has also been shown to regulate transcription by targeting the CDK7/cyclin H subunits of the general transcription initiation factor IIH (TFIIH) thus providing a link between the \' Mediator-like\' protein complexes and the basal transcription machinery. Akoulitchev. S. . et al. . (2000) Nature 407 (6800). 102-106.