TY - JOUR
T1 - A cytoplasmic COMPASS is necessary for cell survival and triple-negative breast cancer pathogenesis by regulating metabolism
AU - Wang, Lu
AU - Collings, Clayton K.
AU - Zhao, Zibo
AU - Cozzolino, Kira Alia
AU - Ma, Quanhong
AU - Liang, Kaiwei
AU - Marshall, Stacy A.
AU - Sze, Christie C.
AU - Hashizume, Rintaro
AU - Savas, Jeffrey Nicholas
AU - Shilatifard, Ali
N1 - Publisher Copyright:
© 2017 Wang et al.
PY - 2017/10/15
Y1 - 2017/10/15
N2 - 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.
AB - 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.
KW - Chromatin
KW - Gene expression
KW - Transcription
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U2 - 10.1101/gad.306092.117
DO - 10.1101/gad.306092.117
M3 - Article
C2 - 29138278
AN - SCOPUS:85035318931
SN - 0890-9369
VL - 31
SP - 2056
EP - 2066
JO - Genes and Development
JF - Genes and Development
IS - 20
ER -