Broek D, Toda T, Michaeli T, Levin L, Birchmeier C, Zoller M, Powers S, Wigler M
Cell. 1987 Mar 13;48(5):789-99. doi: 10.1016/0092-8674(87)90076-6.
The gene corresponding to the S. cerevisiae cell division cycle mutant cdc25 has been cloned and sequenced, revealing an open reading frame encoding a protein of 1589 amino acids that contains no significant homologies with other known proteins. Cells lacking CDC25 have low levels of cyclic AMP and decreased levels of Mg2+-dependent adenylate cyclase activity. The lethality resulting from disruption of the CDC25 gene can be suppressed by the presence of the activated RAS2val19 gene, but not by high copy plasmids expressing a normal RAS2 or RAS1 gene. These results suggest that normal RAS is dependent on CDC25 function. Furthermore, mutationally activated alleles of CDC25 are capable of inducing a set of phenotypes similar to those observed in strains containing a genetically activated RAS/adenylate cyclase pathway, suggesting that CDC25 encodes a regulatory protein. We propose that CDC25 regulates adenylate cyclase by regulating the guanine nucleotide bound to RAS proteins.
与酿酒酵母细胞分裂周期突变体cdc25相对应的基因已被克隆和测序，结果显示一个开放阅读框编码一种含有1589个氨基酸的蛋白质，该蛋白质与其他已知蛋白质没有明显的同源性。缺乏CDC25的细胞中，环磷酸腺苷（cAMP）水平较低，且镁离子依赖性腺苷酸环化酶活性水平降低。CDC25基因破坏导致的致死性可被激活的RAS2val19基因的存在所抑制，但不能被表达正常RAS2或RAS1基因的高拷贝质粒所抑制。这些结果表明正常的RAS依赖于CDC25的功能。此外，CDC25的突变激活等位基因能够诱导出一组类似于在含有基因激活的RAS/腺苷酸环化酶途径的菌株中观察到的表型，这表明CDC25编码一种调节蛋白。我们提出，CDC25通过调节与RAS蛋白结合的鸟嘌呤核苷酸来调节腺苷酸环化酶。
