Transcriptional CDKs and Phosphatases: Keeping RNA Polymerase II on Track and on Time

Cyclin-dependent kinases (CDKs) and protein phosphatases cooperate to regulate transcription by RNA polymerase II (RNAPII). Loss or weakening of this control leads to disordered gene expression and can give rise to cancer. We take chemical-genetic approaches to probe the CDK network and elucidate mechanisms that govern both the cell cycle and transcription. In recent work, we have identified CDK-phosphatase switches that control key transitions in the RNAPII transcription cycle, performed functional dissection of a key factor that tunes the rate of RNAPII elongation, and helped develop a new chemical-genetic tool that targets specially engineered kinases for selective degradation. Finally, we have defined a role in restraining RNAPII elongation, in opposition to CDK activity, for a protein phosphatase complex with tumor-suppressor function in prostate cancer.