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

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 c...

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Autores principales: Wang, Lu, Collings, Clayton K., Zhao, Zibo, Cozzolino, Kira Alia, Ma, Quanhong, Liang, Kaiwei, Marshall, Stacy A., Sze, Christie C., Hashizume, Rintaro, Savas, Jeffrey Nicholas, Shilatifard, Ali
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5733497/
https://www.ncbi.nlm.nih.gov/pubmed/29138278
http://dx.doi.org/10.1101/gad.306092.117
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author Wang, Lu
Collings, Clayton K.
Zhao, Zibo
Cozzolino, Kira Alia
Ma, Quanhong
Liang, Kaiwei
Marshall, Stacy A.
Sze, Christie C.
Hashizume, Rintaro
Savas, Jeffrey Nicholas
Shilatifard, Ali
author_facet Wang, Lu
Collings, Clayton K.
Zhao, Zibo
Cozzolino, Kira Alia
Ma, Quanhong
Liang, Kaiwei
Marshall, Stacy A.
Sze, Christie C.
Hashizume, Rintaro
Savas, Jeffrey Nicholas
Shilatifard, Ali
author_sort Wang, Lu
collection PubMed
description 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.
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spelling pubmed-57334972018-04-15 A cytoplasmic COMPASS is necessary for cell survival and triple-negative breast cancer pathogenesis by regulating metabolism Wang, Lu Collings, Clayton K. Zhao, Zibo Cozzolino, Kira Alia Ma, Quanhong Liang, Kaiwei Marshall, Stacy A. Sze, Christie C. Hashizume, Rintaro Savas, Jeffrey Nicholas Shilatifard, Ali Genes Dev Research Paper 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. Cold Spring Harbor Laboratory Press 2017-10-15 /pmc/articles/PMC5733497/ /pubmed/29138278 http://dx.doi.org/10.1101/gad.306092.117 Text en © 2017 Wang et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Paper
Wang, Lu
Collings, Clayton K.
Zhao, Zibo
Cozzolino, Kira Alia
Ma, Quanhong
Liang, Kaiwei
Marshall, Stacy A.
Sze, Christie C.
Hashizume, Rintaro
Savas, Jeffrey Nicholas
Shilatifard, Ali
A cytoplasmic COMPASS is necessary for cell survival and triple-negative breast cancer pathogenesis by regulating metabolism
title A cytoplasmic COMPASS is necessary for cell survival and triple-negative breast cancer pathogenesis by regulating metabolism
title_full A cytoplasmic COMPASS is necessary for cell survival and triple-negative breast cancer pathogenesis by regulating metabolism
title_fullStr A cytoplasmic COMPASS is necessary for cell survival and triple-negative breast cancer pathogenesis by regulating metabolism
title_full_unstemmed A cytoplasmic COMPASS is necessary for cell survival and triple-negative breast cancer pathogenesis by regulating metabolism
title_short A cytoplasmic COMPASS is necessary for cell survival and triple-negative breast cancer pathogenesis by regulating metabolism
title_sort cytoplasmic compass is necessary for cell survival and triple-negative breast cancer pathogenesis by regulating metabolism
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5733497/
https://www.ncbi.nlm.nih.gov/pubmed/29138278
http://dx.doi.org/10.1101/gad.306092.117
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