Bockstaele Laurence, Coulonval Katia, Kooken Hugues, Paternot Sabine, Roger Pierre P
Institute of Interdisciplinary Research (IRIBHM), Faculté de Médecine, Université Libre de Bruxelles, Campus Erasme, B-1070 Brussels, Belgium.
Cell Div. 2006 Nov 8;1:25. doi: 10.1186/1747-1028-1-25.
Cyclin-dependent kinase (CDK)4 is a master integrator that couples mitogenic and antimitogenic extracellular signals with the cell cycle. It is also crucial for many oncogenic transformation processes. In this overview, we address various molecular features of CDK4 activation that are critical but remain poorly known or debated, including the regulation of its association with D-type cyclins, its subcellular location, its activating Thr172-phosphorylation and the roles of Cip/Kip CDK "inhibitors" in these processes. We have recently identified the T-loop phosphorylation of CDK4, but not of CDK6, as a determining target for cell cycle control by extracellular factors, indicating that CDK4-activating kinase(s) might have to be reconsidered.
细胞周期蛋白依赖性激酶（CDK）4是一个主要的整合因子，它将有丝分裂原性和抗有丝分裂原性细胞外信号与细胞周期联系起来。它对许多致癌转化过程也至关重要。在本综述中，我们探讨了CDK4激活的各种分子特征，这些特征至关重要，但仍鲜为人知或存在争议，包括其与D型细胞周期蛋白结合的调控、亚细胞定位、激活的苏氨酸172磷酸化以及Cip/Kip CDK“抑制剂”在这些过程中的作用。我们最近发现，CDK4而非CDK6的T环磷酸化是细胞外因子控制细胞周期的决定性靶点，这表明可能需要重新考虑CDK4激活激酶。
