USDA Agricultural Research Service, Western Human Nutrition Research Center, University of California at Davis, 430 West Health Science Drive, Davis, CA 95616, USA.
Biochem Biophys Res Commun. 2011 Sep 16;413(1):36-40. doi: 10.1016/j.bbrc.2011.08.032. Epub 2011 Aug 23.
Selenium (Se) is an essential redox-active trace element with close connections to cancer. Most of Se's biological functions have been attributed to the antioxidant properties of Se-containing proteins. However, the relative contribution of selenoproteins and small Se compounds in cancer protection is still a matter of debate. The tumor suppressor p53 is the most frequently mutated gene in human cancer and is often referred to as the "guardian of the genome". In response to genomic stresses, p53 causes cell cycle arrest to allow time for genomic damage to be repaired before cell division or induces apoptosis to eliminate irreparably damaged cells. Selenoprotein W (SEPW1) is a highly conserved small thioredoxin-like protein required for cell cycle progression. The present work shows that SEPW1 facilitates the G1 to S-phase transition by down-regulating expression of the cyclin-dependent kinase inhibitor p21. SEPW1 controls p21 by modulating levels of the p53 transcription factor, and this is associated with changes in phosphorylation of Ser-33 in p53. More work is needed to identify the mechanism by which SEPW1 regulates phosphorylation of Ser-33 and the kinase or phosphatase enzymes involved.
硒（Se）是一种必需的氧化还原活性微量元素，与癌症密切相关。大多数 Se 的生物学功能归因于含硒蛋白的抗氧化特性。然而，硒蛋白和小 Se 化合物在癌症保护中的相对贡献仍然存在争议。肿瘤抑制因子 p53 是人类癌症中最常发生突变的基因，通常被称为“基因组的守护者”。p53 响应基因组应激，导致细胞周期停滞，以便在细胞分裂前有时间修复基因组损伤，或诱导细胞凋亡以消除不可修复的受损细胞。硒蛋白 W（SEPW1）是一种高度保守的小硫氧还蛋白样蛋白，是细胞周期进展所必需的。本研究表明，SEPW1 通过下调细胞周期蛋白依赖性激酶抑制剂 p21 的表达来促进 G1 期到 S 期的转变。SEPW1 通过调节 p53 转录因子的水平来控制 p21，这与 p53 中丝氨酸-33 的磷酸化变化有关。需要进一步的工作来确定 SEPW1 调节丝氨酸-33 磷酸化的机制以及涉及的激酶或磷酸酶酶。
