title: Cyclin C/cdk3 promotes Rb-dependent G0 exit.
abstract: G0 is a physiological state occupied by resting or terminally differentiated cells that have exited the cell cycle. In contrast to the well-characterized cyclin/cdk-mediated inactivation of pRb that controls the G1/S transition, little is known about regulation of the G0/G1 transition. However, pRb is likely to participate in this process because its acute somatic inactivation is sufficient for G0-arrested cells to re-enter the cell cycle. One physiological regulator of this event may be cyclin C because its highest mRNA levels occur during G0 exit. Here we show that a non-cdk8-associated cellular pool of cyclin C combines with cdk3 to stimulate pRb phosphorylation at S807/811 during the G0/G1 transition, and that this phosphorylation is required for cells to exit G0 efficiently. Thus, G1 entry is regulated in an analogous fashion to S phase entry, but involves a distinct cyclin/cdk combination.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Shengjun
authors.initials: S
authors.lastname: Ren
authors.forename: Barrett J
authors.initials: BJ
authors.lastname: Rollins
mesh_terms: D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D056745:Cyclin C; D056849:Cyclin-Dependent Kinase 3; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase / Q000235:genetics / Q000502:physiology; D006801:Humans; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000502:physiology*; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: C503674:CCNC protein, human; D056745:Cyclin C; D016213:Cyclins; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D012694:Serine; C098776:CDK3 protein, human; D056849:Cyclin-Dependent Kinase 3; D018844:Cyclin-Dependent Kinases