Adams P D
Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA.
Biochim Biophys Acta. 2001 Mar 21;1471(3):M123-33. doi: 10.1016/s0304-419x(01)00019-1.
The retinoblastoma tumor suppressor protein (pRB) is a paradigm for understanding cell cycle- and proliferation-dependent transcription and how deregulation of this process contributes to the neoplastic process in humans. The ability of pRB to regulate transcription, and consequently cell proliferation and differentiation, is regulated by the activity of cyclin/cdks. In general, phosphorylation of pRB by cyclin/cdks inactivates pRB-mediated transcriptional inhibition and growth suppression. However, it is apparent that pRB is a multi-functional protein that can inhibit transcription through various mechanisms. This review focuses on recent data to suggest that different pRB functions are progressively and cooperatively inactivated by multiple cyclin/cdk complexes during G1- and S-phase. The implications of such a model for pRB-mediated tumor suppression are discussed.
视网膜母细胞瘤肿瘤抑制蛋白（pRB）是理解细胞周期和增殖依赖性转录以及该过程失调如何导致人类肿瘤发生过程的范例。pRB调节转录从而调控细胞增殖和分化的能力受细胞周期蛋白/细胞周期蛋白依赖性激酶（cyclin/cdks）活性的调节。一般来说，细胞周期蛋白/细胞周期蛋白依赖性激酶使pRB磷酸化会使其介导的转录抑制和生长抑制失活。然而，很明显pRB是一种多功能蛋白，它可以通过多种机制抑制转录。本综述聚焦于近期数据，这些数据表明在G1期和S期，不同的pRB功能被多种细胞周期蛋白/细胞周期蛋白依赖性激酶复合物逐步协同失活。文中还讨论了这种模型对pRB介导的肿瘤抑制的意义。
