Redox regulation of the tumor suppressor PTEN by glutathione

Redox regulation of the tumor suppressor PTEN by glutathione
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DOI:
10.1016/j.febslet.2010.07.006
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发表时间:
2010-08-20
期刊:
影响因子:
3.5
通讯作者:
Lee, Seung-Rock
Lee, Seung-Rock
中科院分区:
生物学3区
文献类型:
--
作者:
Kim, Yujeong;Song, Yong Bhum;Lee, Seung-Rock

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在酿酒酵母中表达的10号染色体上缺失的磷酸酶和张力蛋白同源物(PTEN)被过氧化氢可逆氧化,并被细胞还原剂还原。在S.酿酒酵母gsh 1 δ和gsh 2 δ突变体。γ-谷氨酰半胱氨酸合成酶Gsh 1在gsh 1 Delta突变体中的表达挽救了hPTEN的再生率。氧化的hPTEN被谷胱甘肽以浓度和时间依赖性的方式还原。检测到谷胱甘肽化的PTEN。293 T细胞与BSO共同孵育以及通过siRNA敲低HeLa细胞中GCLc的表达导致氧化型PTEN的还原延迟。此外,在用GCLc siRNA转染的HeLa细胞中,用表皮生长因子刺激导致氧化的PTEN和Akt磷酸化的增加。这些结果表明,氧化的hPTEN的还原是由谷胱甘肽介导的。(C)2010年欧洲生物化学学会联合会。由Elsevier B出版。V.保留所有权利。
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expressed in Saccharomyces cerevisiae was reversibly oxidized by hydrogen peroxide and reduced by cellular reductants. Reduction of hPTEN was delayed in each of S. cerevisiae gsh1 Delta and gsh2 Delta mutants. Expression of gamma-glutamylcysteine synthetase Gsh1 in the gsh1 Delta mutant rescued regeneration rate of hPTEN. Oxidized hPTEN was reduced by glutathione in a concentration-and time-dependent manner. Glutathionylated PTEN was detected. Incubation of 293T cells with BSO and knockdown expression of GCLc in HeLa cells by siRNA resulted in the delay of reduction of oxidized PTEN. Also, in HeLa cells transfected with GCLc siRNA, stimulation with epidermal growth factor resulted in the increase of oxidized PTEN and phosphorylation of Akt. These results suggest that the reduction of oxidized hPTEN is mediated by glutathione. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.