MacLachlan T K, Sang N, Giordano A
Jefferson Cancer Institute, Department of Microbiology/Immunology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Crit Rev Eukaryot Gene Expr. 1995;5(2):127-56. doi: 10.1615/critreveukargeneexpr.v5.i2.20.
A significant portion of cell scientific literature published is dedicated to describing the cloning, the link to cancer, or the characterization of proteins involved in the progression of the cell cycle. With this abundance of information, the cascading pathways of molecular events that occur in the cell cycle are proving to be exceedingly complicated. Originally, the sole regulator of the fission yeast cells division cycle, cdc2, was thought to also regulate mammalian cell cycles in the same manner. However, mammalian cdc2 has now been joined by seven well-characterized relatives acting at distinct points in the cell cycle. These kinases are activated by larger proteins called cyclins, named with respect to their cyclical expression and degradation. Therefore, the catalytic subunits of these complexes are named cyclin-dependent kinases (cdks). In the event that the cell must stop normal cycling behavior, a number of cdk inhibitors, which have only begun to be characterized, function in inhibiting the kinase ability of cdks, among other nonproliferative acts. The external environment manipulates cellular proliferation and differentiation by stimulating or inhibiting certain signal transduction pathways. However, each component of the cell cycle machinery, as they are the final executors in cell division, has the potential to elicit or to contribute to a neoplastic phenotype. This review focuses on the characterization of each member of the cell cycle protein family and also addresses the potential role each plays in cancer.
已发表的细胞科学文献中有很大一部分致力于描述细胞周期进程中所涉及蛋白质的克隆、与癌症的关联或特性。鉴于信息如此丰富，细胞周期中发生的分子事件的级联途径被证明极其复杂。最初，裂殖酵母细胞分裂周期的唯一调节因子cdc2被认为也以同样的方式调节哺乳动物细胞周期。然而，现在哺乳动物的cdc2已经有了七个特征明确的亲属，它们在细胞周期的不同阶段发挥作用。这些激酶由称为细胞周期蛋白的更大蛋白质激活，细胞周期蛋白因其周期性表达和降解而得名。因此，这些复合物的催化亚基被命名为细胞周期蛋白依赖性激酶（cdk）。如果细胞必须停止正常的循环行为，一些刚刚开始被表征的cdk抑制剂除了其他非增殖作用外，还具有抑制cdk激酶活性的功能。外部环境通过刺激或抑制某些信号转导途径来操纵细胞增殖和分化。然而，细胞周期机制的每个组成部分，由于它们是细胞分裂的最终执行者，都有可能引发或促成肿瘤表型。本综述重点介绍细胞周期蛋白家族每个成员的特性，并探讨它们在癌症中可能发挥的作用。
