Myb-related Schizosaccharomyces pombe cdc5p is structurally and functionally conserved in eukaryotes
Myb-related Schizosaccharomyces pombe cdc5p is structurally and functionally conserved in eukaryotes
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DOI：
10.1128/mcb.18.7.4097
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发表时间：
1998-07-01
影响因子：
5.3
通讯作者：
Gould, KL
中科院分区：
文献类型：
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作者：
Ohi, R;Feoktistova, A;Gould, KL
Schizosaccharomyces pombe cdc5p是一种myb相关蛋白，对G(2)/M进展至关重要。为了探索Cdc5在进化过程中的结构和功能保守性，我们从酿酒酵母、秀丽隐杆线虫、黑腹果蝇和黑腹果蝇中分离出Cdc5相关基因和cdna。和智人。支持这些Cdc5基因家族成员在功能上与S. pombe Cdc5（+）同源的观点，人类和苍蝇的Cdc5 cdna能够补充S. pombe Cdc5 -120突变体的温度敏感致死性。此外，酿酒葡萄球菌CEF1（酿酒葡萄球菌cdc5+的同源物）与pompe cdc5（+）一样，在G(2)/M期间是必不可少的。cdc5-120突变的位置以及Cef1p的突变分析表明，cddp和Cef1p的Myb重复序列对它们在体内的功能很重要。然而，我们听起来不像c-Myb；在Cef1p的Myb重复序列中，甘氨酸单残基取代疏水残基是维持Myb结构域结构所必需的，这并不会损害Cef1p在体内的功能。相反，需要多次W-to-G替换来灭活Cef1p，并且发现许多替换突变体具有温度敏感性；虽然Cef1p可能作为转录激活因子，但我们已经证明Cef1p不参与一类以SWI5为典型的G(2)/ m调节基因的转录激活。总的来说，这些结果表明Cdc5家族成员参与调节G(2)/M进展的新途径。
Schizosaccharomyces pombe cdc5p is a Myb-related protein that is essential for G(2)/M progression. To explore the structural and functional conservation of Cdc5 throughout evolution, we isolated Cdc5-retated genes and cDNAs from Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster; and Homo sapiens. Supporting the notion that these Cdc5 gene family members are functionally homologous to S. pombe cdc5(+), human and fly Cdc5 cDNAs are capable of complementing the temperature-sensitive lethality of the S. pombe cdc5-120 mutant. Furthermore, S. cerevisiae CEF1 (S. cerevisiae homolog of cdc5+), like S. pompe cdc5(+), is essential during G(2)/M. The location of the cdc5-120 mutation, as well as mutational analyses of Cef1p, indicate that the Myb repeats of cddp and Cef1p are important for their function in vivo. However, we Sound that unlike in c-Myb; single residue substitutions of glycines for hydrophobic residues within the Myb repeats of Cef1p, which are essential for maintaining structure of the Myb domain, did not impair Cef1p function in vivo. Rather, multiple W-to-G substitutions were required to inactivate Cef1p, and many of the substitution mutants were found to confer temperature sensitivity; Although it is possible that Cef1p acts as a transcriptional activator, we have demonstrated that Cef1p is not involved in transcriptional activation of a class of G(2)/M-regulated genes typified by SWI5. Collectively, these results suggest that Cdc5 family members participate in a novel pathway to regulate G(2)/M progression.