Interaction between cyclin T1 and SCF^SKP2 targets CDK9 for ubiquitination and degradation by the proteasome

CDK9 paired with cyclin T1 forms the human P-TEFb complex and stimulates productive transcription through phosphorylation of the RNA polymerase II C-terminal domain. Here we report that CDK9 is ubiquitinated and degraded by the proteasome whereas cyclin T1 is stable. SCF^SKP2 was recruited to CDK9/cyclin T1 via cyclin T1 in an interaction requiring its PEST domain. CDK9 ubiquitination was modulated by cyclin T1 and p45^SKP2. CDK9 accumulated in p45^SKP2-/- cells, and its expression during the cell cycle was periodic. The transcriptional activity of CDK9/cyclin T1 on the class II major histocompatibility complex promoter could be regulated by CDK9 degradation in vivo. We propose a novel mechanism whereby recruitment of SCF^SKP2 is mediated by cyclin T1 while ubiquitination occurs exclusively on CDK9.