Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Supplemental material
  • Version history
  • Article usage
  • Citations to this article
Advertisement

ResearchIn-Press PreviewEndocrinology Open Access | 10.1172/jci.insight.151390

ARMC5-CUL3 E3 ligase targets full-length SREBF in adrenocortical tumor

Yosuke Okuno,1 Atsunori Fukuhara,1 Michio Otsuki,1 and Iichiro Shimomura1

1Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Japan

Find articles by Okuno, Y. in: JCI | PubMed | Google Scholar

1Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Japan

Find articles by Fukuhara, A. in: JCI | PubMed | Google Scholar |

1Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Japan

Find articles by Otsuki, M. in: JCI | PubMed | Google Scholar |

1Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Japan

Find articles by Shimomura, I. in: JCI | PubMed | Google Scholar

Published July 21, 2022 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.151390.
Copyright © 2022, Okuno et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published July 21, 2022 - Version history
View PDF
Abstract

Inactivating mutations of ARMC5 are responsible for the development of bilateral macronodular adrenal hyperplasia (BMAH). Although ARMC5 inhibits adrenocortical tumor growth and is considered as tumor-suppressor gene, its molecular function is poorly understood. In this study, through biochemical purification using SREBF (SREBP) as bait, we identified the interaction between SREBF and ARMC5 through its Armadillo repeat. We also found that ARMC5 interacted with CUL3 through its BTB domain and underwent self-ubiquitination. ARMC5 colocalized with SREBF1 in the cytosol and induced proteasome-dependent degradation of full-length SREBF through ubiquitination. Introduction of missense mutations in Armadillo repeat of ARMC5 attenuated the interaction between SREBF, and introduction of mutations found in BMAH completely abolished its ability to degrade full-length SREBF. In H295R adrenocortical cells, silencing of ARMC5 increased full-length SREBFs and upregulated SREBF2 target genes. siARMC5-mediated cell growth was abrogated by simultaneous knockdown of SREBF2 in H295R cells. Our results demonstrated that ARMC5 was a substrate adaptor protein between full-length SREBF and CUL3-based E3 ligase, and suggested the involvement of SREBF pathway in the development of BMAH.

Graphical Abstract
graphical abstract
Supplemental material

View

Version history
  • Version 1 (July 21, 2022): In-Press Preview

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Supplemental material
  • Version history
Advertisement
Advertisement

Copyright © 2022 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts