Chiarugi V, Magnelli L, Cinelli M, Basi G
Laboratory of Molecular Biology, University of Florence, Firenze, Italy.
Cell Mol Biol Res. 1994;40(7-8):603-12.
This brief review examines the strict relationships between cell apoptosis and G1 cyclins. It has been shown that the basic role of G1 cyclins is in regulating G1 progression and G1/S transition (the critical cycle point for cell program decisions, including apoptosis) a fatal program for cells unable to bypass G1/S checkpoint 1. Notably, both of the two giant regulators of checkpoint 1 (i.e., p105RB [retinoblastoma oncosuppressor-encoded protein] and p53 dependent WAF1/CIP1) are influenced by or influence G1 cyclins: cyclin E/cdk2 kinase complexes hyperphosphorylate p105RB, induce E2F release, and free G1 exit. On the other hand, p21-WAF1/CIP1 is an inhibitor of cyclin-dependent kinases blocking cells at G1/S. Thus, G1 cyclin activity appears as a conditio sine qua non for G1 exit and apoptosis escape.
本简要综述探讨了细胞凋亡与G1期细胞周期蛋白之间的紧密关系。研究表明，G1期细胞周期蛋白的基本作用是调节G1期进程和G1/S期转换（这是细胞程序决定的关键周期点，包括细胞凋亡，对于无法绕过G1/S期检查点1的细胞来说是一个致命程序）。值得注意的是，检查点1的两个主要调节因子（即p105RB[视网膜母细胞瘤抑癌基因编码蛋白]和p53依赖的WAF1/CIP1）都受到G1期细胞周期蛋白的影响或对其产生影响：细胞周期蛋白E/细胞周期蛋白依赖性激酶2（cyclin E/cdk2）激酶复合物使p105RB过度磷酸化，诱导E2F释放，并使细胞自由退出G1期。另一方面，p21-WAF1/CIP1是一种细胞周期蛋白依赖性激酶抑制剂，可将细胞阻滞在G1/S期。因此，G1期细胞周期蛋白的活性似乎是细胞退出G1期和逃避凋亡的必要条件。
