Cables1 protects p63 from proteasomal degradation to ensure deletion of cells after genotoxic stress.
Cables1 protects p63 from proteasomal degradation to ensure deletion of cells after genotoxic stress.
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DOI：
10.1038/embor.2010.82
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发表时间：
2010-08
期刊：
影响因子：
7.7
通讯作者：
Tilly, Jonathan L.
中科院分区：
文献类型：
--
作者：
Wang, Ning;Guo, Lankai;Rueda, Bo R.;Tilly, Jonathan L.
Cables1与TAp63相互作用，以保护其在暴露于遗传毒性应激后免受泛素介导的降解。缺乏Cables1的卵母细胞在响应遗传毒性应激时积累较少的磷酸化TAp63，这增强了这些细胞的存活。p63基因产物调节上皮形态发生和雌性生殖系完整性。在这项研究中，我们发现细胞周期蛋白依赖性激酶5和Abl酶底物1（Cables1）与反式激活（TA）p63α亚型相互作用，以保护其免受蛋白酶体降解。使用Cables1基因敲除小鼠的雌性生殖系作为体内模型，我们进一步证明了缺乏Cables1的卵母细胞在响应遗传毒性应激时表现出较低的TAp63α基础水平和减少的磷酸化TAp63α积累。这反过来又增强了电离辐射暴露后这些细胞的存活。因此，电缆1调节p63蛋白的稳定性和功能，在遗传毒性应激。
Cables1 interacts with TAp63 to protect it from ubiquitin-mediated degradation after exposure to genotoxic stress. Oocytes lacking Cables1 accumulate less phosphorylated TAp63 in response to genotoxic stress, which enhances the survival of these cells. The p63 gene product regulates epithelial morphogenesis and female germline integrity. In this study, we show that cyclin-dependent kinase 5 and Abl enzyme substrate 1 (Cables1) interacts with the trans-activating (TA) p63α isoform to protect it from proteasomal degradation. Using the female germline of Cables1-null mice as an in vivo model, we demonstrate further that oocytes lacking Cables1 exhibit lower basal levels of TAp63α and reduced accumulation of phosphorylated TAp63α in response to genotoxic stress. This in turn enhances the survival of these cells after ionizing radiation exposure. Thus, Cables1 modulates p63 protein stability and function during genotoxic stress.
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影响因子：
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