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A cytoplasmic COMPASS is necessary for cell survival and triple-negative breast cancer pathogenesis by regulating metabolism

Authors :
Lu Wang
Rintaro Hashizume
Ali Shilatifard
Jeffrey N. Savas
Quanhong Ma
Kira A. Cozzolino
Zibo Zhao
Clayton K. Collings
Stacy A. Marshall
Kaiwei Liang
Christie C. Sze
Source :
Genes & Development. 31:2056-2066
Publication Year :
2017
Publisher :
Cold Spring Harbor Laboratory, 2017.

Abstract

Mutations and translocations within the COMPASS (complex of proteins associated with Set1) family of histone lysine methyltransferases are associated with a large number of human diseases, including cancer. Here we report that SET1B/COMPASS, which is essential for cell survival, surprisingly has a cytoplasmic variant. SET1B, but not its SET domain, is critical for maintaining cell viability, indicating a novel catalytic-independent role of SET1B/COMPASS. Loss of SET1B or its unique cytoplasmic-interacting protein, BOD1, leads to up-regulation of expression of numerous genes modulating fatty acid metabolism, including ADIPOR1 (adiponectin receptor 1), COX7C, SDC4, and COQ7. Our detailed molecular studies identify ADIPOR1 signaling, which is inactivated in both obesity and human cancers, as a key target of SET1B/COMPASS. Collectively, our study reveals a cytoplasmic function for a member of the COMPASS family, which could be harnessed for therapeutic regulation of signaling in human diseases, including cancer.

Details

ISSN :
15495477 and 08909369
Volume :
31
Database :
OpenAIRE
Journal :
Genes & Development
Accession number :
edsair.doi.dedup.....4bb3916e005f77b56e0cd1732cb20fc4
Full Text :
https://doi.org/10.1101/gad.306092.117