Aligue R, Akhavan-Niak H, Russell P
Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037.
EMBO J. 1994 Dec 15;13(24):6099-106. doi: 10.1002/j.1460-2075.1994.tb06956.x.
Wee1 protein kinase regulates the length of G2 phase by carrying out the inhibitory tyrosyl phosphorylation of Cdc2-cyclin B kinase. Mutations were isolated that suppressed the G2 cell cycle arrest caused by overproduction of Wee1. One class of swo (suppressor of wee1 overproduction) mutation, exemplified by swo1-26, also caused a temperature sensitive lethal phenotype in a wee1+ background. The swo1+ gene encodes a member of the Hsp90 family of stress proteins. Swo1 is essential for viability at all temperatures. Swo1 coimmunoprecipitates with Wee1, showing that the two proteins interact. The swo1-26 mutant undergoes premature mitosis when grown at a semi-permissive temperature. These data strongly indicate that formation of active Wee1 tyrosine kinase requires interaction with Swo1, perhaps in a manner analogous to the previously demonstrated interaction between Hsp90 and v-src tyrosine kinase. These observations demonstrate a unexpected role for Hsp90 in cell cycle control.
Wee1蛋白激酶通过对Cdc2-细胞周期蛋白B激酶进行抑制性酪氨酸磷酸化来调节G2期的时长。分离出了一些能抑制因Wee1过量产生而导致的G2期细胞周期阻滞的突变。一类swo（wee1过量产生的抑制子）突变，以swo1-26为例，在wee1+背景下也会导致温度敏感致死表型。swo1+基因编码应激蛋白Hsp90家族的一个成员。Swo1在所有温度下对于细胞存活都是必需的。Swo1与Wee1进行共免疫沉淀，表明这两种蛋白相互作用。swo1-26突变体在半允许温度下生长时会经历过早的有丝分裂。这些数据强烈表明，活性Wee1酪氨酸激酶的形成需要与Swo1相互作用，可能是以一种类似于先前证明的Hsp90与v-src酪氨酸激酶之间相互作用的方式。这些观察结果证明了Hsp90在细胞周期调控中具有意想不到的作用。
