Fischer Joshua L, Lancia Jody K, Mathur Anita, Smith Martin L
Indiana University School of Medicine, Department of Microbiology, Walther Oncology Center, Walther Cancer Institute, Indianapolis, IN 46202, USA.
Anticancer Res. 2006 Mar-Apr;26(2A):899-904.
Selenium, in the form of seleno-L-methionine (SeMet), induced Redox-factor-1 (Ref1) and p53 proteins in normal human and mouse fibroblasts. Ref1 and p53 are known to be associated with each other, resulting in enhanced sequence-specific DNA binding by p53 and transactivation of p53-regulated effector genes. SeMet preferentially induced the DNA repair branch of the p53 pathway, while apoptosis and cell cycle arrest were unaffected. Accordingly, pretreatment with SeMet protected normal fibroblasts from subsequent DNA damage. In the current study, Brca1 and Ref1 were shown to interact concurrently with p53 in targeting a SeMet-induced DNA repair response. Moreover, like p53 and Ref1, Brca1 was required for SeMet-mediated DNA damage protection, as brca1 -/- mouse fibroblasts were not protected from UV-radiation by SeMet treatment. These findings indicate that besides p53 and Ref1, Brca1 is required for selenium protection from DNA damage. The data are consistent with selective induction of the DNA repair branch of the p53 pathway by SeMet.
以硒代-L-蛋氨酸（SeMet）形式存在的硒，可在正常人和小鼠成纤维细胞中诱导氧化还原因子1（Ref1）和p53蛋白。已知Ref1和p53相互关联，导致p53增强序列特异性DNA结合以及p53调节的效应基因的反式激活。SeMet优先诱导p53途径的DNA修复分支，而细胞凋亡和细胞周期停滞未受影响。因此，用SeMet预处理可保护正常成纤维细胞免受后续DNA损伤。在当前研究中，Brca1和Ref1被证明在靶向SeMet诱导的DNA修复反应中与p53同时相互作用。此外，与p53和Ref1一样，Brca1是SeMet介导的DNA损伤保护所必需的，因为brca1 -/-小鼠成纤维细胞经SeMet处理后不能免受紫外线辐射。这些发现表明，除了p53和Ref1之外，Brca1也是硒保护免受DNA损伤所必需的。这些数据与SeMet对p53途径的DNA修复分支的选择性诱导一致。
