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iScience. 2019 May 31;15:196-210. doi: 10.1016/j.isci.2019.04.027. Epub 2019 Apr 26.

PBRM1 Regulates Stress Response in Epithelial Cells.

Author information

1
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47906, USA.
2
Department of Biochemistry, Purdue University, West Lafayette, IN 47906, USA.
3
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47906, USA. Electronic address: edykhui@purdue.edu.

Abstract

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.

KEYWORDS:

Cancer; Molecular Mechanism of Behavior; Molecular Mechanism of Gene Regulation

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