Porter Elizabeth G, Dhiman Alisha, Chowdhury Basudev, Carter Benjamin C, Lin Hang, Stewart Jane C, Kazemian Majid, Wendt Michael K, Dykhuizen Emily C
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47906, USA.
Department of Biochemistry, Purdue University, West Lafayette, IN 47906, USA.
iScience. 2019 May 31;15:196-210. doi: 10.1016/j.isci.2019.04.027. Epub 2019 Apr 26.
Polybromo1 (PBRM1) is a chromatin remodeler subunit highly mutated in cancer, particularly clear cell renal carcinoma. PBRM1 is a member of the SWI/SNF subcomplex, PBAF (PBRM1-Brg1/Brm-associated factors), and is characterized by six tandem bromodomains. Here we establish a role for PBRM1 in epithelial cell maintenance through the expression of genes involved in cell adhesion, metabolism, stress response, and apoptosis. In support of a general role for PBRM1 in stress response and apoptosis, we observe that loss of PBRM1 results in an increase in reactive oxygen species generation and a decrease in cellular viability under stress conditions. We find that loss of PBRM1 promotes cell growth under favorable conditions but is required for cell survival under conditions of cellular stress.
多溴蛋白1（PBRM1）是一种染色质重塑亚基，在癌症中高度突变，尤其是在透明细胞肾细胞癌中。PBRM1是SWI/SNF亚复合物PBAF（PBRM1 - Brg1/Brm相关因子）的成员，其特征是具有六个串联的溴结构域。在这里，我们通过参与细胞粘附、代谢、应激反应和凋亡的基因表达，确定了PBRM1在上皮细胞维持中的作用。为支持PBRM1在应激反应和凋亡中的一般作用，我们观察到PBRM1的缺失导致活性氧生成增加，并且在应激条件下细胞活力降低。我们发现，PBRM1的缺失在有利条件下促进细胞生长，但在细胞应激条件下是细胞存活所必需的。
