Nuclear localization of Cdc25 is regulated by DNA damage and a 14-3-3 protein
Nuclear localization of Cdc25 is regulated by DNA damage and a 14-3-3 protein
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DOI：
10.1038/16488
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发表时间：
1999-01-14
期刊：
影响因子：
64.8
通讯作者：
Russell, P
中科院分区：
文献类型：
--
作者：
Lopez-Girona, A;Furnari, B;Russell, P
DNA损伤激活细胞周期检查点，在DNA修复进行时阻止有丝分裂（1）。Chk 1蛋白通过磷酸化有丝分裂诱导剂Cdc 25来执行该检查点（参考文献2-6），Chk 1对Cdc 25的磷酸化在Cdc 25中产生14-3-3蛋白的结合位点（5-8），但尚不清楚14-3-3蛋白如何调节Cdc 25。Rad 24是一种14-3-3蛋白，在裂变酵母的DNA损伤检查点中很重要（9）。在这里，我们表明，Rad 24控制Cdc 25的细胞内分布。消除Rad 24导致Cdc 25的核积累。DNA损伤检查点的激活导致Cdc 25的净核输出，这一过程需要Chk 1，Rad 24和核输出机制。Rad 24中假定的核输出信号的突变损害Rad 24的核排斥、Cdc 25的损伤诱导的核输出和损伤检查点。因此，Rad 24似乎作为一个附加的核输出信号，增强了Cdc 25的核输出响应DNA损伤。
DNA damage activates a cell-cycle checkpoint that prevents mitosis while DNA repair is under way(1). The protein Chk1 enforces this checkpoint by phosphorylating the mitotic inducer Cdc25 (refs 2-6), Phosphorylation of Cdc25 by Chk1 creates a binding site in Cdc25 for 14-3-3 proteins(5-8), but it is not known how 14-3-3 proteins regulate Cdc25. Rad24 is a 14-3-3 protein that is important in the DNA-damage checkpoint in fission yeast(9). Here we show that Rad24 controls the intracellular distribution of Cdc25. Elimination of Rad24 causes nuclear accumulation of Cdc25. Activation of the DNA-damage checkpoint causes the net nuclear export of Cdc25 by a process that requires Chk1, Rad24 and nuclear-export machinery. Mutation of a putative nuclear-export signal in Rad24 impairs the nuclear exclusion of Rad24, the damage-induced nuclear export of Cdc25 and the damage checkpoint. Thus, Rad24 appears to function as an attachable nuclear-export signal that enhances the nuclear export of Cdc25 in response to DNA damage.