D-TYPE CYCLINS

D-type cyclins couple extracellular signals to the biochemical machine ry that governs progression through G1 phase of the mammalian cell div ision cycle. Induced by growth factor stimulation, D-type cyclins asse mble with cyclin-dependent kinases CDK4 and CDK6 to form holoenzymes t hat facilitate exit from G1 by phosphorylating key substrates, includi ng the retinoblastoma protein. Activation of the holoenzymes is antago nized by polypeptide inhibitors of CDK activity, which are induced by antiproliferative signals. Once cells pass a late G1 restriction point , cyclin-D-dependent kinases are unnecessary for completion of the cel l cycle, implying that their primary role is to sense the cell's readi ness to replicate DNA and to enforce the commitment to enter S phase.