CDK-ACTIVATING KINASE COMPLEX IS A COMPONENT OF HUMAN TRANSCRIPTION FACTOR TFIIH

TRANSCRIPTION factor IIH (TFIIH) contains a kinase capable of phosphor ylating the carboxy-terminal domain (CTD) of the largest subunit of RN A polymerase II (RNAPII)1-3. Here we report the identification of the Cdk-activating kinase (Cak) complex (Cdk7 and cyclin H) as a component of TFIIH after extensive purification of TFIIH by chromatography. We find that affinity-purified antibodies directed against cyclin H inhib it TFIIH-dependent transcription and that both cyclin H and Cdk7 antib odies inhibit phosphorylation of the CTD of the largest subunit of the RNAPII in the preinitiation complex. Cak is present in at least two d istinct complexes, TFIIH and a smaller complex that is unable to phosp horylate RNAPII in the preinitiation complex. Both Cak complexes, as w ell as recombinant Cak, phosphorylate a CTD peptide. Finally, TFIIH wa s shown to phosphorylate both Cdc2 and Cdk2, suggesting that there cou ld be a link between transcription and the cell cycle machinery.