Lee M G, Norbury C J, Spurr N K, Nurse P
ICRF Cell Cycle Control Laboratory, Department of Biochemistry, Oxford, UK.
Nature. 1988 Jun 16;333(6174):676-9. doi: 10.1038/333676a0.
A novel approach to the study of the control of the mammalian cell cycle was opened by the cloning of a human gene by complementation of a fission-yeast cdc2 cell-cycle mutant. We have investigated the behaviour of the RNA and protein products of this human gene, CDC2Hs, and its murine equivalent, CDC2Mm during serum starvation and re-feeding of cultured fibroblasts. In contrast to the pattern of wild-type cdc2+ expression in fission yeast previously described, the mammalian homologue displays variation in both RNA and protein levels during exit from and re-entry into the mitotic cycle. Like its yeast counterpart, however, the mammalian CDC2 protein (p34CDC2) becomes dephosphorylated upon shifting from exponential growth to quiescence, and rephosphorylated late in the G1 phase when cells are stimulated to re-enter the cycle. We propose that phosphorylation of p34CDC2 serves as a regulatory mechanism generally in eukaryotic cells, while transcriptional control of the CDC2 gene in higher eukaryotes may be relevant to long term processes such as senescence and differentiation.
通过对裂殖酵母 cdc2 细胞周期突变体进行互补克隆人类基因，开启了一种研究哺乳动物细胞周期调控的新方法。我们研究了该人类基因 CDC2Hs 及其小鼠同源基因 CDC2Mm 的 RNA 和蛋白质产物在培养的成纤维细胞血清饥饿和重新喂食过程中的行为。与先前描述的裂殖酵母中野生型 cdc2+ 的表达模式不同，哺乳动物同源物在退出和重新进入有丝分裂周期时，RNA 和蛋白质水平均有变化。然而，与酵母对应物一样，哺乳动物 CDC2 蛋白（p34CDC2）在从指数生长转变为静止状态时会去磷酸化，并在 G1 期后期细胞被刺激重新进入周期时再次磷酸化。我们提出，p34CDC2 的磷酸化通常作为真核细胞中的一种调节机制，而高等真核生物中 CDC2 基因的转录控制可能与衰老和分化等长期过程有关。
