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首页> 外文期刊>Molecular and Cellular Biology >B56 Regulatory Subunit of Protein Phosphatase 2A Mediates Valproic Acid-Induced p300 Degradation
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B56 Regulatory Subunit of Protein Phosphatase 2A Mediates Valproic Acid-Induced p300 Degradation

机译：B56蛋白质磷酸酶2A的调节亚基介导丙戊酸诱导的P300降解

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Transcriptional coactivator p300 is required for embryonic development and cell proliferation. Valproic acid, a histone deacetylase inhibitor, is widely used in the therapy of epilepsy and bipolar disorder. However, it has intrinsic teratogenic activity through unidentified mechanisms. We report that valproic acid stimulates proteasome-dependent p300 degradation through augmentation of gene expression of the B56γ regulatory subunits of protein phosphatase 2A. The B56γ3 regulatory and catalytic subunits of protein phosphatase 2A interact with p300. Overexpression of the B56γ3 subunit leads to proteasome-mediated p300 degradation and represses p300-dependent transcriptional activation, which requires the B56γ3 interaction domain of p300. Conversely, silencing of the B56γ subunit expression by RNA interference increases the stability and transcriptional activity of the coactivator. Our study establishes the functional interaction between protein phosphatase 2A and p300 activity and provides direct evidence for signal-dependent control of p300 function.
机译：胚胎发育和细胞增殖需要转录调用剂P300。丙戊酸，一种组蛋白脱乙酰酶抑制剂广泛用于癫痫和双相障碍的治疗。然而，通过未识别的机制，它具有内在的致畸活性。我们认为羟甲酸刺激蛋白酶体依赖性P300降解通过增强蛋白质磷酸酶2a的B56γ调节亚基的基因表达。蛋白质磷酸酶2a的B56γ3调节和催化亚基与P300相互作用。 B56γ3亚基的过表达导致蛋白酶体介导的P300降解并抑制P300依赖性转录活化，这需要P300的B56γ3相互作用域。相反，通过RNA干扰的B56γ亚基表达的沉默增加了共觉器的稳定性和转录活性。我们的研究建立了蛋白质磷酸酶2a和p300活性之间的功能相互作用，并提供了P300功能的信号依赖性控制的直接证据。

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