REGULATED EXPRESSION AND PHOSPHORYLATION OF A POSSIBLE MAMMALIAN CELL-CYCLE CONTROL PROTEIN

REGULATED EXPRESSION AND PHOSPHORYLATION OF A POSSIBLE MAMMALIAN CELL-CYCLE CONTROL PROTEIN
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DOI:
10.1038/333676a0
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发表时间:
1988-06-16
期刊:
影响因子:
64.8
通讯作者:
NURSE, P
NURSE, P
中科院分区:
综合性期刊1区
文献类型:
--
作者:
LEE, MG;NORBURY, CJ;NURSE, P

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通过互补裂变酵母cdc2细胞周期突变体1克隆人类基因,开辟了研究哺乳动物细胞周期控制的新方法。我们研究了这种人类基因 CDC2Hs 及其小鼠基因 CDC2Mm 的 RNA 和蛋白质产物在血清饥饿和培养成纤维细胞重新喂养期间的行为。与先前描述的裂殖酵母中野生型cdc2+表达模式相反2,3,哺乳动物同源物在退出和重新进入有丝分裂周期期间表现出RNA和蛋白质水平的变化。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时变得去磷酸化,并在G1期后期当细胞被刺激重新进入周期时重新磷酸化。我们认为p34CDC2的磷酸化通常在真核细胞中充当调节机制,而高等真核细胞中CDC2基因的转录控制可能与衰老和分化等长期过程相关。
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-yeastcdc2cell-cycle mutant1. 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-typecdc2+expression in fission yeast previously described2,3, 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 mammalianCDC2protein (p34CDC2) becomes dephosphorylated upon shifting from exponential growth to quiescence, and rephosphorylated late in the Glphase when cells are stimulated to re-enter the cycle. We propose that phosphorylation of p34CDC2serves as a regulatory mechanism generally in eukaryotic cells, while transcriptional control of theCDC2gene in higher eukaryotes may be relevant to long term processes such as senescence and differentiation.