Li Y, Nichols M A, Shay J W, Xiong Y
Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill 27599-3280.
Cancer Res. 1994 Dec 1;54(23):6078-82.
Progression of the eukaryotic cell division cycle is regulated by a series of structurally related serine/threonine protein kinases known as cyclin-dependent kinases (CDKs). The D-type cyclin-dependent kinases, CDK4 and CDK6, have been strongly implicated in the control of G1 progression and the phosphorylation of the retinoblastoma protein, pRb. The formation of complexes and enzymatic activity of cyclin D-CDK4 and cyclin D-CDK6 kinases is negatively regulated by p16INK4 (MTS1/CDK4I/CDKN2) via its specific interaction with CDK4 and CDK6 catalytic subunits. Here we report that the p16 mRNA accumulates to a high level in cells lacking pRb function and transcription of p16 is repressed by pRb. Our results provide evidence supporting a feedback regulatory loop involving pRb, p16, and cyclin-dependent kinases.
真核细胞分裂周期的进程受一系列结构相关的丝氨酸/苏氨酸蛋白激酶调控，这些激酶被称为细胞周期蛋白依赖性激酶（CDK）。D型细胞周期蛋白依赖性激酶CDK4和CDK6与G1期进程的控制及视网膜母细胞瘤蛋白pRb的磷酸化密切相关。细胞周期蛋白D-CDK4和细胞周期蛋白D-CDK6激酶的复合物形成及酶活性受到p16INK4（MTS1/CDK4I/CDKN2）的负调控，p16INK4通过与CDK4和CDK6催化亚基的特异性相互作用发挥作用。在此我们报告，p16 mRNA在缺乏pRb功能的细胞中积累至高水平，且pRb可抑制p16的转录。我们的结果提供了证据，支持涉及pRb、p16和细胞周期蛋白依赖性激酶的反馈调节环。
