Additional Functions
In addition to activating Cdks, CAK also regulates transcription. Two forms of CAK have been identified: free CAK and associated CAK. Free CAK is quantitatively predominant compared to associated CAK. Free CAK phosphorylates Cdks and is involved in cell cycle regulation. Associated CAK is part of the general transcription factor TFIIH. CAK associated with TFIIH phosphorylates proteins involved in transcription including RNA polymerase II. More specifically, associated CAK is involved in promoter clearance and progression of transcription from the preinitiation to the initiation stage.
In vertebrates, the trimeric CAK complex is responsible for transcription regulation. In budding yeast, the Cdk7 homolog, Kin28, regulates transcription. In fission yeast, the Msc6 Msc2 complex controls basal gene transcription.
In addition to regulating transcription, CAK also enhances transcription by phosphorylating retinoic acid and estrogen receptors. Phosphorylation of these receptors leads to increased expression of target genes. In leukemic cells, where DNA is damaged, CAK’s ability to phosphorylate retinoic acid and estrogen receptors is decreased. Decreased CAK activity creates a feedback loop, which turns off TFIIH activity.
CAK also plays a role in DNA damage response. The activity of CAK associated with TFIIH decreases when DNA is damaged by UV irradiation. Inhibition of CAK prevents cell cycle from progressing. This mechanism ensures the fidelity of chromosome transmission.
Read more about this topic: CDK-activating Kinase
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