Park Yong Hwan, Jeon Yeong Ha, Kim Ick Young
Laboratory of Cellular and Molecular Biochemistry, School of Life Sciences and Biotechnology, Korea University, 1, 5-Ka, Anam-Dong, Sungbuk-Ku, Seoul 136-701, Republic of Korea.
Biochim Biophys Acta. 2012 Dec;1823(12):2217-26. doi: 10.1016/j.bbamcr.2012.09.001. Epub 2012 Sep 12.
Selenoprotein W (SelW) contains a highly reactive selenocysteine (Sec; U) in the CXXU motif corresponding to the CXXC motif in thioredoxin (Trx) and thus it appears to be involved in regulating the cellular redox state. Recent reports on the interaction between SelW and 14-3-3 suggest that SelW may be redox dependently involved in the cell cycle. However, the precise function of SelW has not yet been elucidated. Here, we show that SelW is involved in the G2-M transition, especially in the recovery from G2 arrest after deoxyribonucleic acid (DNA) damage. Knockdown of SelW significantly accumulated phosphorylated cyclin-dependent kinase (Cdk1), which eventually led to a delay in recovery from G2 arrest. We also found that inactive Cdk1 is caused by the sustained inactivation of CDC25B, which removes the inhibitory phosphate from Cdk1. Our observation from this study reveals that SelW activated CDC25B by promoting the dissociation of 14-3-3 from CDC25B through the reduction of the intramolecular disulfide bond during recovery. We suggest that SelW plays an important role in the recovery from G2 arrest by determining the dissociation of 14-3-3 from CDC25B in a redox-dependent manner.
硒蛋白W（SelW）在CXXU基序中含有一个高度反应性的硒代半胱氨酸（Sec；U），该基序与硫氧还蛋白（Trx）中的CXXC基序相对应，因此它似乎参与调节细胞氧化还原状态。最近关于SelW与14-3-3相互作用的报道表明，SelW可能以氧化还原依赖的方式参与细胞周期。然而，SelW的确切功能尚未阐明。在这里，我们表明SelW参与G2-M期转换，特别是在DNA损伤后从G2期阻滞中恢复的过程。敲低SelW会显著积累磷酸化的细胞周期蛋白依赖性激酶（Cdk1），最终导致从G2期阻滞中恢复延迟。我们还发现，无活性的Cdk1是由CDC25B的持续失活引起的，CDC25B可去除Cdk1上的抑制性磷酸基团。我们从这项研究中的观察结果表明，在恢复过程中，SelW通过还原分子内二硫键促进14-3-3从CDC25B上解离，从而激活CDC25B。我们认为，SelW通过以氧化还原依赖的方式决定14-3-3从CDC25B上解离，在从G2期阻滞中恢复的过程中发挥重要作用。
