Lange Bodo M H, Rebollo Elena, Herold Andrea, González Cayetano
European Molecular Biology Laboratory, Cell Biology and Biophysics Programme and Gene Expression Programme, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
EMBO J. 2002 Oct 15;21(20):5364-74. doi: 10.1093/emboj/cdf531.
Cdc37 has been shown to be required for the activity and stability of protein kinases that regulate different stages of cell cycle progression. However, little is known so far regarding interactions of Cdc37 with kinases that play a role in cell division. Here we show that the loss of function of Cdc37 in Drosophila leads to defects in mitosis and male meiosis, and that these phenotypes closely resemble those brought about by the inactivation of Aurora B. We provide evidence that Aurora B interacts with and requires the Cdc37/Hsp90 complex for its stability. We conclude that the Cdc37/Hsp90 complex modulates the function of Aurora B and that most of the phenotypes brought about by the loss of Cdc37 function can be explained by the inactivation of this kinase. These observations substantiate the role of Cdc37 as an upstream regulatory element of key cell cycle kinases.
已证明Cdc37是调节细胞周期进程不同阶段的蛋白激酶的活性和稳定性所必需的。然而，迄今为止，关于Cdc37与在细胞分裂中起作用的激酶之间的相互作用知之甚少。在这里，我们表明果蝇中Cdc37的功能丧失会导致有丝分裂和雄性减数分裂缺陷，并且这些表型与Aurora B失活所导致的表型非常相似。我们提供的证据表明，Aurora B与Cdc37/Hsp90复合物相互作用，并需要该复合物来维持其稳定性。我们得出结论，Cdc37/Hsp90复合物调节Aurora B的功能，并且Cdc37功能丧失所导致的大多数表型可以通过该激酶的失活来解释。这些观察结果证实了Cdc37作为关键细胞周期激酶的上游调节元件的作用。
