CDC25A IS A NOVEL PHOSPHATASE FUNCTIONING EARLY IN THE CELL-CYCLE

CDC25A IS A NOVEL PHOSPHATASE FUNCTIONING EARLY IN THE CELL-CYCLE
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DOI:
10.1002/j.1460-2075.1994.tb06417.x
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发表时间:
1994-04-01
期刊:
影响因子:
11.4
通讯作者:
OKAYAMA, H
OKAYAMA, H
中科院分区:
生物学1区
文献类型:
--
作者:
JINNO, S;SUTO, K;OKAYAMA, H

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cdc25(+) 酪氨酸磷酸酶是裂殖酵母裂殖酵母的小桶有丝分裂诱导剂,控制有丝分裂起始的时间。哺乳动物至少含有三种 cdc25(+) 同源物,称为 cdc25A、cdc25B 和 cdc25C。在本研究中,我们研究了 cdc25A 的生物学功能。尽管 cdc25A 在拯救粟酒裂殖酵母 cdc25 突变体方面非常有效,但在结构上与裂殖酵母酶的相关性较低。 Northern 和 Western blotting 检测表明,与 cdc25B、cdc25C 和 cdc2 不同,cdc25A 主要在 G1 晚期表达。此外,通过激光扫描单细胞细胞术测定,通过显微注射特定抗体对大鼠细胞中的 cdc25A 进行免疫耗竭,可有效阻止其细胞周期从 G1 期进入 S 期。这些结果表明cdc25A不是有丝分裂调节剂,而是一种新型磷酸酶,在细胞周期的启动中起着至关重要的作用。鉴于其激活 cdc2 激酶的强大能力及其在 G1 晚期的特异性表达,在细胞周期早期发挥作用的 cdc2 相关激酶可能是该磷酸酶的靶点。
The cdc25(+) tyrosine phosphatase is a keg mitotic inducer of the fission yeast Schizosaccharomyces pombe, controlling the timing of the initiation of mitosis. Mammals contain at least three cdc25(+) homologues called cdc25A, cdc25B and cdc25C. in this study we investigate the biological function of cdc25A. Although very potent in rescuing the S.pombe cdc25 mutant, cdc25A is less structurally related to the S.pombe enzyme. Northern and Western blotting detection reveals that unlike cdc25B, cdc25C and cdc2, cdc25A is predominantly expressed in late G1. Moreover, immunodepletion of cdc25A in rat cells by microinjection of a specific antibody effectively blocks their cell cycle progression from G1 into the S phase, as determined by laser scanning single cell cytometry. These results indicate that cdc25A is not a mitotic regulator but a novel phosphatase that plays a crucial role in the start of the cell cycle. In view of its strong ability to activate cdc2 kinase and its specific expression in late G1, cdc2-related kinases functioning early in the cell cycle may be targets for this phosphatase.