Liu Xueni, Ehmed Elphire, Li Boyao, Dou Jianming, Qiao Xiaojing, Jiang Wenyong, Yang Xi, Qiao Shouyi, Wu Yanhua
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University Shanghai 200438, P. R. China.
Am J Cancer Res. 2016 Jun 1;6(6):1441-9. eCollection 2016.
Breast cancer metastasis suppressor 1 (BRMS1) is a specific tumor metastasis suppressor implicated in the regulation of chromatin modification and gene transcription. However, the molecular mechanism of BRMS1 remains to be elucidated. Here, we report that DBC1 (deleted in breast cancer 1), is a novel interacting protein of BRMS1. The imperfect leucine zipper motifs of BRMS1 and the N-terminal domain of DBC1 are required for the interaction. DBC1 is identified as an important negative regulator of SIRT1's activity and genotoxic stress response. We demonstrated that BRMS1 is able to interrupt endogenous DBC1-SIRT1 association. Consistently, SIRT1-dependent p53 acetylation under genotoxic stress is also affected by BRMS1. Overall, our results identify BRMS1 as a novel regulator of DBC1-SIRT1 complex and SIRT1-dependent p53 deacetylation.
乳腺癌转移抑制因子1（BRMS1）是一种特定的肿瘤转移抑制因子，参与染色质修饰和基因转录的调控。然而，BRMS1的分子机制仍有待阐明。在此，我们报告称，乳腺癌缺失基因1（DBC1）是BRMS1的一种新型相互作用蛋白。BRMS1的不完全亮氨酸拉链基序和DBC1的N端结构域是这种相互作用所必需的。DBC1被确定为沉默信息调节因子1（SIRT1）活性和基因毒性应激反应的重要负调节因子。我们证明，BRMS1能够中断内源性DBC1-SIRT1关联。同样，基因毒性应激下依赖SIRT1的p53乙酰化也受到BRMS1的影响。总体而言，我们的结果确定BRMS1是DBC1-SIRT1复合物和依赖SIRT1的p53去乙酰化的新型调节因子。
