Format

Send to

Choose Destination
Genes Dev. 2017 Oct 15;31(20):2056-2066. doi: 10.1101/gad.306092.117. Epub 2017 Nov 14.

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

Author information

1
Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
2
Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
3
Department of Neurosurgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
4
Robert H. Lurie National Cancer Institute Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.

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.

KEYWORDS:

chromatin; gene expression; transcription

PMID:
29138278
PMCID:
PMC5733497
DOI:
10.1101/gad.306092.117
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center