A mammalian homolog of fission yeast Cdc5 regulates G2 progression and mitotic entry

A mammalian homolog of fission yeast Cdc5 regulates G2 progression and mitotic entry
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DOI:
10.1074/jbc.273.8.4666
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发表时间:
1998-02-20
影响因子:
4.8
通讯作者:
Coughlin, SR
Coughlin, SR
中科院分区:
生物学2区
文献类型:
--
作者:
Bernstein, HS;Coughlin, SR

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通过哺乳动物细胞分裂周期的G2/M的进展需要许多基因产物的协调表达,但很少有人知道的转录调控参与。粟酒裂殖酵母Cdc 5是一个与G2/M期转换有关的转录因子,最近发现了一个编码人Cdc 5的cDNA,命名为hCdc 5。粟酒霉Cdc 5. hCdc 5在人类组织中的广泛表达以及与其他真核生物中表达序列的同源性表明了一种进化上保守的一般功能,在哺乳动物细胞的血清刺激下,hCdc 5的核输入表明了在细胞增殖中的可能作用,我们现在报道了hCdc 5在哺乳动物细胞中的过表达缩短了G2并减小了细胞大小,缺乏羧基末端激活结构域的hCdc 5显性负突变体减慢了G2期进程并延迟进入有丝分裂,因此,hCdc 5是第一个显示影响哺乳动物细胞G2期进程和有丝分裂进入的转录调节因子。
Progression through G2/M of the mammalian cell division cycle requires the coordinated expression of many gene products, but little is known of the transcriptional regulators involved. Schizosaccharomyces pombe Cdc5 is a putative transcription factor implicated in G2/M transit, me recently identified a cDNA encoding a putative human transcription factor, now designated human Cdc5 (hCdc5), with homology to S. pombe Cdc5. Widespread expression of hCdc5 in human tissues and homology with expressed sequences in other eukaryotes suggested an evolutionarily conserved general function, Nuclear import of hCdc5 upon serum stimulation of mammalian cells suggested a possible role in cell proliferation, We now report that overexpression of hCdc5 in mammalian cells shortened G2 and reduced cell size, A dominant negative mutant of hCdc5 lacking the carboxyl-terminal activation domain slowed G2 progression and delayed entry into mitosis, Thus, hCdc5 is the first transcriptional regulator shown to affect G2 progression and mitotic entry in mammalian cells.