Department of Pediatrics; Department of Biochemistry and Molecular Pharmacology; Imbalzano Lab; Nickerson Lab
Biochemistry, Biophysics, and Structural Biology | Cancer Biology | Cell Biology | Genetics and Genomics
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.
ADAADi, BRG1, BRM, PFI-3, breast cancer, cancer metabolism, chromatin remodeling, drug transporters, mammalian SWI/SNF enzymes
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© Anthony N. Imbalzano.
DOI of Published Version
Epigenomics. 2017 Jun;9(6):919-931. doi: 10.2217/epi-2017-0034. Epub 2017 May 19. Link to article on publisher's site
Wu Q, Lian JB, Stein JL, Stein GS, Nickerson JA, Imbalzano AN. (2017). The BRG1 ATPase of human SWI/SNF chromatin remodeling enzymes as a driver of cancer. Pediatric Publications. https://doi.org/10.2217/epi-2017-0034. Retrieved from https://escholarship.umassmed.edu/peds_pp/155
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