THE RB FAMILY CONTAINS A CONSERVED CYCLIN-DEPENDENT KINASE-REGULATED TRANSCRIPTIONAL REPRESSOR MOTIF

Progression through the cell cycle is dependent on the sequential expr ession of cyclins, which combine with cyclin-dependent kinases (cdks) to form active kinases. The transition from G(1) to S phase is depende nt on D cyclins in complex with cdk4 or cdk6 and cyclin E complexed wi th cdk2. One target of G(1) cyclins is the retinoblastoma susceptibili ty protein (Rb). Rb is a transcriptional repressor that is selectively targeted to genes through interaction with the E2F family of cell cyc le transcription factors. Rb is a member of a family of proteins that include p107 and p130. The three proteins share a region known as the pocket that is important for binding E2F and is also the binding site for oncoproteins from DNA tumor viruses that inactivate Rb. We have fo und that two conserved domains within the Rb pocket (A and B) interact to form a transcriptional repressor motif (K. N. B. Chow and D. C. De an, Mol. Cell. Biol. 16:4862-4868, 1996). Here we demonstrate that p10 7 also has an A-B repressor motif, and using domain swapping and coimm unoprecipitation assays, we compare A and B from Rb and p107. Finally and most importantly, we demonstrate that the A-B interaction which fo rms the repressor motif is blocked by G(1) cdk phosphorylation, thereb y blocking repressor activity. This A-B repressor motif is then the fi rst example of a cdk-regulated transcriptional repressor.