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Review
. 2017 Jun;9(6):919-931.
doi: 10.2217/epi-2017-0034. Epub 2017 May 19.

The BRG1 ATPase of human SWI/SNF chromatin remodeling enzymes as a driver of cancer

Qiong Wu  1 , Jane B Lian  2 , Janet L Stein  2 , Gary S Stein  2 , Jeffrey A Nickerson  1 , Anthony N Imbalzano  3
Affiliations
Review

The BRG1 ATPase of human SWI/SNF chromatin remodeling enzymes as a driver of cancer

Qiong Wu et al. Epigenomics. 2017 Jun.

Abstract

Mammalian SWI/SNF enzymes are ATP-dependent remodelers of chromatin structure. These multisubunit enzymes are heterogeneous in composition; there are two catalytic ATPase subunits, BRM and BRG1, that are mutually exclusive, and additional subunits are incorporated in a combinatorial manner. Recent findings indicate that approximately 20% of human cancers contain mutations in SWI/SNF enzyme subunits, leading to the conclusion that the enzyme subunits are critical tumor suppressors. However, overexpression of specific subunits without apparent mutation is emerging as an alternative mechanism by which cellular transformation may occur. Here we highlight recent evidence linking elevated expression of the BRG1 ATPase to tissue-specific cancers and work suggesting that inhibiting BRG1 may be an effective therapeutic strategy.

Keywords: ADAADi; BRG1; BRM; PFI-3; breast cancer; cancer metabolism; chromatin remodeling; drug transporters; mammalian SWI/SNF enzymes.

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Conflict of interest statement

Financial & competing interests disclosure

The authors and this work were supported by National Institutes of Health grants P01 CA82834 and R21 CA185926. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Figures

<b>Figure 1.</b>
Figure 1.. Domain structure of BRG1.
Conserved domains are labeled. Numbers across the top of the schematic represent amino acids.
<b>Figure 2.</b>
Figure 2.. Pathways implicated in BRG1 function in tumors and cancer cell lines showing elevated levels of BRG1.
See text for details.
See this image and copyright information in PMC

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