Inactivation of the Cdc25 phosphatase by the stress-activated Srk1 kinase in fission yeast
Inactivation of the Cdc25 phosphatase by the stress-activated Srk1 kinase in fission yeast
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DOI：
10.1016/j.molcel.2004.11.043
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发表时间：
2005-01-07
期刊：
影响因子：
16
通讯作者：
Aligue, R
中科院分区：
文献类型：
--
作者：
López-Avilés, S;Grande, M;Aligue, R
环境压力调节细胞周期进程的机制知之甚少。在裂殖酵母中，我们发现Srk 1激酶与应激激活的p38/Sty 1 MAP激酶相关，通过抑制Cdc 25磷酸酶调节有丝分裂的发生。Srk 1在G2期周期性活跃，其过表达导致细胞周期停滞在G2晚期，而缺乏Srk 1的细胞过早进入有丝分裂。我们发现，Srk 1相互作用和磷酸化Cdc 25在相同的网站磷酸化的Chk 1和Cds 1（Chk 2）激酶，这种磷酸化是必要的Srk 1延迟有丝分裂进入。Srk 1的磷酸化导致Cdc 25与14-3-3蛋白家族成员Rad 24结合，并使Cdc 25在细胞质中积累。然而，Srk 1不调节Cdc 25在复制停滞或DNA损伤，而是在正常的细胞周期和响应非遗传毒性的环境压力。
The mechanisms by which environmental stress regulates cell cycle progression are poorly understood. In fission yeast, we show that Srk1 kinase, which associates with the stress-activated p38/Sty1 MAP kinase, regulates the onset of mitosis by inhibiting the Cdc25 phosphatase. Srk1 is periodically active in G2, and its overexpression causes cell cycle arrest in late G2 phase, whereas cells lacking srk1 enter mitosis prematurely. We find that Srk1 interacts with and phosphorylates Cdc25 at the same sites phosphorylated by the Chk1 and Cds1 (Chk2) kinases and that this phosphorylation is necessary for Srk1 to delay mitotic entry. Phosphorylation by Srk1 causes Cdc25 to bind to Rad24, a 14-3-3 protein family member, and accumulation of Cdc25 in the cytoplasm. However, Srk1 does not regulate Cdc25 in response to replication arrest or DNA damage but, rather, during a normal cell cycle and in response to nongenotoxic environmental stress.