Phosphorylation and stabilization of TAp63γ by IκB kinase-β
Phosphorylation and stabilization of TAp63γ by IκB kinase-β
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DOI：
10.1074/jbc.m801394200
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发表时间：
2008-06-06
影响因子：
4.8
通讯作者：
Lu, Hua
中科院分区：
文献类型：
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作者：
MacPartlin, Mary;Zeng, Shelya X.;Lu, Hua
P53家族成员的翻译后修饰是其调控的关键。在这里，我们报道了I kappa B激酶β(Ikk Beta)对TAp63γ的磷酸化，而不是Delta Np63 Gamma的磷酸化。γ射线或肿瘤坏死因子-α激活IKKβ可导致细胞内TAp63γ蛋白水平升高。IKKβ，而不是它的激酶缺陷突变体IKKβ-K44A，导致了TAp63伽马的这种稳定。在没有IKKβ的情况下，TAp63伽马对伽马辐射的这种稳定性显著降低。TAp63γ的磷酸化可阻止泛素化和该蛋白可能的降解。我们推测，IKKβ对TAp63伽马的磷酸化通过阻止TAp63伽马蛋白泛素化依赖的降解来稳定TAp63伽马蛋白。
Post-translational modification of the p53 family members is key to their regulation. Here we report the phosphorylation of TAp63 gamma, but not Delta Np63 gamma, by I kappa B kinase beta (IKK beta). Activation of IKK beta by gamma radiation or tumor necrosis factor-alpha led to increased TAp63 gamma protein levels in cells. IKK beta, but not its kinase-defective mutant IKK beta-K44A, led to this observed stabilization of TAp63 gamma. This stabilization of TAp63 gamma in response to gamma radiation was significantly decreased in the absence of IKK beta. Phosphorylation of TAp63 gamma blocks ubiquitylation and possible degradation of this protein. We postulate that phosphorylation of TAp63 gamma by IKK beta stabilizes the TAp63 gamma protein by blocking ubiquitylation-dependent degradation of this protein.