PBRM1 Regulates Stress Response in Epithelial Cells

Summary 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.
Graphical Abstract
Highlights • PBRM1 facilitates the expression of stress response genes in epithelial cells • Deletion of PBRM1 promotes growth under low-stress conditions • PBRM1 restrains ROS generation and induces apoptosis under high-stress conditions • Under H2O2 stress, PBRM1 cooperates with cJun and NRF2 to induce gene expression
Molecular Mechanism of Gene Regulation; Molecular Mechanism of Behavior; Cancer