Protein cysteine sulfinic acid reductase (sulfiredoxin) as a regulator of cell proliferation and drug response
Protein cysteine sulfinic acid reductase (sulfiredoxin) as a regulator of cell proliferation and drug response
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DOI：
10.1038/onc.2008.132
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发表时间：
2008-08-21
期刊：
影响因子：
8
通讯作者：
Tew, K. D.
中科院分区：
文献类型：
--
作者：
Lei, K.;Townsend, D. M.;Tew, K. D.
硫氧还蛋白(SRX)是一类与维持细胞氧化还原平衡有关的低分子含硫蛋白家族。SRX的一个功能是在氧化应激下将蛋白质中的半胱氨酸亚磺酸还原为亚磺酸。其他氧化还原活性蛋白家族在调节氧化还原和控制增殖/死亡途径方面具有多种功能；SRX的增加与致癌转化有关。为了探索SRX在肿瘤中的生物学功能，我们建立了过表达SRX的细胞系。顺铂后SRX水平的升高促进了细胞的增殖和细胞的死亡。SRX的过表达引发了细胞周期调节因子p21、p27和p53的表达和磷酸化的改变；稳定了磷酸酶PTEN，更重要的是，直接与磷酸酶PTP1B相互作用并增强了其活性。反过来，这通过使其抑制酪氨酸残基去磷酸化来促进Src激酶的活性(Y530)。细胞暴露于一定的生长因子可刺激SRX的表达。这些数据支持SRX通过对磷酸酶活性的影响来控制关键调节蛋白激酶的磷酸化状态，最终影响影响细胞增殖的途径。
Sulfiredoxin (Srx) is one of a family of low molecular weight sulfur containing proteins linked with maintenance of cellular redox balance. One function of Srx is the reduction of cysteine sulfinic acid to sulfenic acid in proteins subject to oxidative stress. Other redox active protein families have multiple functions in regulating redox and controlling proliferation/death pathways; increased Srx has been linked with oncogenic transformation. To explore the biological functions of Srx in tumors, we established cell lines that overexpress Srx. Enhanced levels of Srx promoted cell proliferation and enhanced cell death following cisplatin. Srx overexpression triggered an alteration in expression and phosphorylation of cell cycle regulators p21, p27 and p53; stabilized the phosphatase PTEN and, importantly, interacted directly with, and enhanced the activity of, phosphatase PTP1B. In turn, this promoted Src kinase activity by dephosphorylating its inhibitory tyrosine residue (Y530). Srx expression was stimulated by cell exposure to certain growth factors. These data support a role for Srx in controlling the phosphorylation status of key regulatory kinases through effects upon phosphatase activity with an ultimate effect on pathways that influence cell proliferation.