Ataxia Telangiectasia-mutated- and Rad3-related Protein Regulates the DNA Damage-induced G2/M Checkpoint through the Aurora A Cofactor Bora Protein
Ataxia Telangiectasia-mutated- and Rad3-related Protein Regulates the DNA Damage-induced G2/M Checkpoint through the Aurora A Cofactor Bora Protein
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共济失调毛细血管扩张突变和 Rad3 相关蛋白通过 Aurora A 辅因子 Bora 蛋白调节 DNA 损伤诱导的 G2/M 检查点
DOI：
10.1074/jbc.m113.456780
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发表时间：
2013-05-31
影响因子：
4.8
通讯作者：
Lou, Zhenkun
中科院分区：
文献类型：
--
作者：
Qin, Bo;Gao, Bowen;Lou, Zhenkun
Polo-like kinase1(Plk1)的激活受到DNA损伤的抑制，这种抑制有助于G(2)/M检查点的激活，尽管Plk1被抑制的分子机制尚不清楚。在此，我们报道了DNA损伤信号通路通过BORA抑制Plk1的活性。紫外线照射后，共济失调毛细血管扩张突变和RAD3相关蛋白使Bora在Thr-501处磷酸化。随后，磷酸化的Thr-501被E3泛素连接酶SCF-beta-TRCP识别，该酶针对BORA进行降解。BORA的降解影响了Plk1的激活，并导致DNA损伤导致G(2)期停滞。这些发现为Plk1通过DNA损伤反应途径进行调控提供了新的线索。
Polo-like kinase1 (Plk1) activation is inhibited in response to DNA damage, and this inhibition contributes to the activation of the G(2)/M checkpoint, although the molecular mechanism by which Plk1 is inhibited is not clear. Here we report that the DNA damage signaling pathway inhibits Plk1 activity through Bora. Following UV irradiation, ataxia telangiectasia-mutated-and Rad3-related protein phosphorylates Bora at Thr-501. The phosphorylated Thr-501 is subsequently recognized by the E3 ubiquitin ligase SCF-beta-TRCP, which targets Bora for degradation. The degradation of Bora compromises Plk1 activation and contributes to DNA damage-induced G(2) arrest. These findings shed new light on Plk1 regulation by the DNA damage response pathway.