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A cytoplasmic COMPASS is necessary for cell survival and triple-negative breast cancer pathogenesis by regulating metabolism
- 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.
- Subjects :
- 0301 basic medicine
Cytoplasm
animal structures
Methyltransferase
Cell Survival
Mice, Nude
Cell Cycle Proteins
Triple Negative Breast Neoplasms
Biology
Mice
03 medical and health sciences
Cytochrome P-450 Enzyme System
Cell Line, Tumor
Gene expression
Genetics
Animals
Humans
Gene
Triple-negative breast cancer
Adiponectin receptor 1
Histone-Lysine N-Methyltransferase
Cell biology
Chromatin
PR-SET Domains
Protein Subunits
030104 developmental biology
Histone
MCF-7 Cells
biology.protein
Receptors, Adiponectin
Research Paper
Signal Transduction
Developmental Biology
Subjects
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