Editing Cyclin-dependent kinase complex (section)

====G<sub>1</sub> to S phase progression====
During late G<sub>1</sub> phase, CDKCs bind and phosphorylate members of the [[Retinoblastoma protein|retinoblastoma (Rb) protein]] family.  Members of the Rb protein family are tumor suppressors, which prevent uncontrolled cell proliferation that would occur during tumor formation.  However, pRbs are also thought to repress the genes required in order for the transition from G<sub>1</sub> phase to S phase to occur.  When the cell is ready to transition into the next phase, CDKCs, cyclin D1-Cdk4 and cyclin D1-Cdk6 phosphorylate pRB, followed by additional phosphorylation from the cyclin E-Cdk2 CDKC.<ref>Mittnacht S.  Control of pRB phosphorylation.  Curr Opin Genet Dev. 1998 Feb;8(1):21-7.</ref><ref>Kaelin WG Jr.  Functions of the retinoblastoma protein.  Bioessays. 1999 Nov;21(11):950-8.</ref>  Once phosphorylation occurs, [[transcription factor]]s are then released to irreversibly inactivate pRB and progression into the S phase of the cell cycle ensues.<ref>Lundberg AS, Weinberg RA.  Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes.  Mol Cell Biol. 1998 Feb;18(2):753-61.</ref>  The [[Cyclin E/Cdk2|cyclin E-Cdk2]] CDKC formed in the G<sub>1</sub> phase then aids in the initiation of DNA replication during S phase.<ref name=Malumbres />