Malumbres M, Ortega S, Barbacid M
Molecular Oncology Program, Centro Nacional de Investigaciones Oncológicas Carlos III, Madrid, Spain.
Biol Chem. 2000 Sep-Oct;381(9-10):827-38. doi: 10.1515/BC.2000.105.
Entry into the cell cycle, in particular the G1/S transition, is a tightly regulated process that involves a combination of mitogenic signaling pathways and cell cycle checkpoints. Some of the key regulators of this process are frequently altered in human cancer. Although the proteins that control the G1/S transition have been extensively studied at the biochemical level, little is known regarding their physiological role in vivo. During the last few years, a series of mouse strains carrying gene targeted mutations in key regulators of the G1/S transition have been generated. They include the Rb family of proteins and some of their downstream and upstream regulators. The latter include the regulatory (cyclin) and catalytic (Cdk) subunits of some of the kinases responsible for Rb inactivation as well as all the members of two families of cell cycle inhibitors, the INK4 and the Cip/Kip proteins. In this review, we summarize the most relevant information derived from the characterization of these strains of mice and attempt to integrate it within a functional framework of cell cycle regulation in vivo.
进入细胞周期，尤其是G1/S期转换，是一个受到严格调控的过程，涉及有丝分裂信号通路和细胞周期检查点的共同作用。这一过程的一些关键调节因子在人类癌症中常常发生改变。尽管在生化水平上对控制G1/S期转换的蛋白质进行了广泛研究，但对它们在体内的生理作用却知之甚少。在过去几年中，已经培育出了一系列在G1/S期转换关键调节因子中携带基因靶向突变的小鼠品系。它们包括Rb蛋白家族及其一些下游和上游调节因子。后者包括一些负责使Rb失活的激酶的调节（细胞周期蛋白）和催化（细胞周期蛋白依赖性激酶，Cdk）亚基，以及细胞周期抑制剂两个家族的所有成员，即INK4蛋白家族和Cip/Kip蛋白家族。在这篇综述中，我们总结了从这些小鼠品系的特征中获得的最相关信息，并试图将其整合到体内细胞周期调控的功能框架中。
