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

Lu Wang, Clayton K. Collings, Zibo Zhao, Kira Alia Cozzolino, Quanhong Ma, Kaiwei Liang, Stacy A. Marshall, Christie C. Sze, Rintaro Hashizume, Jeffrey Nicholas Savas, Ali Shilatifard*

*Corresponding author for this work

Research output: Contribution to journalArticle

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2056-2066
Number of pages11
JournalGenes and Development
Volume31
Issue number20
DOIs
Publication statusPublished - Oct 15 2017

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Keywords

  • Chromatin
  • Gene expression
  • Transcription

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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