Sherr C J
Howard Hughes Medical Institute, Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Trends Biochem Sci. 1995 May;20(5):187-90. doi: 10.1016/s0968-0004(00)89005-2.
D-type cyclins couple extracellular signals to the biochemical machinery that governs progression through G1 phase of the mammalian cell division cycle. Induced by growth factor stimulation, D-type cyclins assemble with cyclin-dependent kinases CDK4 and CDK6 to form holoenzymes that facilitate exit from G1 by phosphorylating key substrates, including the retinoblastoma protein. Activation of the holoenzymes is antagonized 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 cell cycle, implying that their primary role is to sense the cell's readiness to replicate DNA and to enforce the commitment to enter S phase.
D型细胞周期蛋白将细胞外信号与调控哺乳动物细胞分裂周期G1期进程的生化机制联系起来。在生长因子刺激下诱导产生的D型细胞周期蛋白与细胞周期蛋白依赖性激酶CDK4和CDK6组装形成全酶，该全酶通过磷酸化包括视网膜母细胞瘤蛋白在内的关键底物来促进细胞从G1期退出。CDK活性的多肽抑制剂可拮抗全酶的激活，这些抑制剂由抗增殖信号诱导产生。一旦细胞通过G1期晚期限制点，细胞周期的完成就不再需要细胞周期蛋白D依赖性激酶，这意味着它们的主要作用是感知细胞复制DNA的准备情况并促使细胞进入S期。
