Skip to main content
Advertisement
  • Other Publications
    • EMBO Press
    • The EMBO Journal (Home)
    • EMBO reports
    • EMBO Molecular Medicine
    • Molecular Systems Biology
    • Life Science Alliance
Login

   

Search

Advanced Search

Journal

  • Home
  • Latest Online
  • Current Issue
  • Archive
  • Subject Collections
  • Review Series & Focuses

Authors & Referees

  • Submit
  • Author Guidelines
  • Aims & Scope
  • Editors & Board
  • Transparent Process
  • Bibliometrics
  • Referee Guidelines
  • Open Access Charges

Info

  • E-Mail Editorial Office
  • Alerts
  • RSS Feeds
  • Subscriptions & Access
  • Reprints & Permissions
  • Advertise & Sponsor
  • Media Partners
  • News & Press
  • Recommend to Librarian
  • Customer Service
  • Home
  • The EMBO Journal: 37 (18)

Source Data

Transparent Process

Article

CRL4AMBRA1 targets Elongin C for ubiquitination and degradation to modulate CRL5 signaling

Si‐Han Chen, Gwendolyn M Jang, Ruth Hüttenhain, David E Gordon, View ORCID ProfileDan Du, Billy W Newton, Jeffrey R Johnson, Joseph Hiatt, Judd F Hultquist, Tasha L Johnson, Yi‐Liang Liu, Lily A Burton, Jordan Ye, Kurt M Reichermeier, Robert M Stroud, Alexander Marson, Jayanta Debnath, View ORCID ProfileJohn D Gross, View ORCID ProfileNevan J Krogan
DOI 10.15252/embj.201797508 | Published online 30.08.2018
The EMBO Journal (2018) 37, e97508
Si‐Han Chen
Department of Cellular and Molecular Pharmacology, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA, USABiophysics Graduate Program, University of California, San Francisco, San Francisco, CA, USAQuantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USAGladstone Institutes, San Francisco, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gwendolyn M Jang
Department of Cellular and Molecular Pharmacology, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA, USAQuantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USAGladstone Institutes, San Francisco, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ruth Hüttenhain
Department of Cellular and Molecular Pharmacology, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA, USAQuantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USAGladstone Institutes, San Francisco, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David E Gordon
Department of Cellular and Molecular Pharmacology, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA, USAQuantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USAGladstone Institutes, San Francisco, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dan Du
Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Billy W Newton
Department of Cellular and Molecular Pharmacology, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA, USAQuantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USAGladstone Institutes, San Francisco, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jeffrey R Johnson
Department of Cellular and Molecular Pharmacology, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA, USAQuantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USAGladstone Institutes, San Francisco, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joseph Hiatt
Medical Scientist Training Program, University of California, San Francisco, San Francisco, CA, USABiomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, USADepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USADiabetes Center, University of California, San Francisco, San Francisco, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Judd F Hultquist
Department of Cellular and Molecular Pharmacology, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA, USAQuantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USAGladstone Institutes, San Francisco, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tasha L Johnson
Department of Cellular and Molecular Pharmacology, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA, USAQuantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USAGladstone Institutes, San Francisco, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yi‐Liang Liu
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lily A Burton
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jordan Ye
Department of Pathology, University of California, San Francisco, San Francisco, CA, USAHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kurt M Reichermeier
California Institute of Technology, Pasadena, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert M Stroud
Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USADepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alexander Marson
Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USADepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USADiabetes Center, University of California, San Francisco, San Francisco, CA, USADivision of Infectious Diseases and Rheumatology, University of California, Berkeley, Berkeley, CA, USAInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USAChan Zuckerberg Biohub, San Francisco, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jayanta Debnath
Department of Pathology, University of California, San Francisco, San Francisco, CA, USAHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John D Gross
Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USADepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nevan J Krogan
Department of Cellular and Molecular Pharmacology, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA, USAQuantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USAGladstone Institutes, San Francisco, CA, USAHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site

Author Affiliations

  1. Si‐Han Chen1,2,3,4,
  2. Gwendolyn M Jang1,3,4,
  3. Ruth Hüttenhain1,3,4,
  4. David E Gordon1,3,4,
  5. Dan Du5,
  6. Billy W Newton1,3,4,
  7. Jeffrey R Johnson1,3,4,
  8. Joseph Hiatt6,7,8,9,
  9. Judd F Hultquist1,3,4,
  10. Tasha L Johnson1,3,4,
  11. Yi‐Liang Liu10,
  12. Lily A Burton11,
  13. Jordan Ye12,13,
  14. Kurt M Reichermeier14,
  15. Robert M Stroud3,10,
  16. Alexander Marson3,8,9,15,16,17,
  17. Jayanta Debnath12,13,
  18. John D Gross3,11 and
  19. Nevan J Krogan (nevan.krogan{at}ucsf.edu)*,1,3,4,13
  1. 1Department of Cellular and Molecular Pharmacology, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA, USA
  2. 2Biophysics Graduate Program, University of California, San Francisco, San Francisco, CA, USA
  3. 3Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA
  4. 4Gladstone Institutes, San Francisco, CA, USA
  5. 5Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA, USA
  6. 6Medical Scientist Training Program, University of California, San Francisco, San Francisco, CA, USA
  7. 7Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, USA
  8. 8Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA
  9. 9Diabetes Center, University of California, San Francisco, San Francisco, CA, USA
  10. 10Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA
  11. 11Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA
  12. 12Department of Pathology, University of California, San Francisco, San Francisco, CA, USA
  13. 13Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA
  14. 14California Institute of Technology, Pasadena, CA, USA
  15. 15Division of Infectious Diseases and Rheumatology, University of California, Berkeley, Berkeley, CA, USA
  16. 16Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA
  17. 17Chan Zuckerberg Biohub, San Francisco, CA, USA
  1. ↵*Corresponding author. Tel: +1 415 476 2980; E‐mail: nevan.krogan{at}ucsf.edu
View Full Text
  • Article
  • Figures & Data
  • Transparent Process
Loading

Abstract

Multi‐subunit cullin‐RING ligases (CRLs) are the largest family of ubiquitin E3 ligases in humans. CRL activity is tightly regulated to prevent unintended substrate degradation or autocatalytic degradation of CRL subunits. Using a proteomics strategy, we discovered that CRL4AMBRA1 (CRL substrate receptor denoted in superscript) targets Elongin C (ELOC), the essential adapter protein of CRL5 complexes, for polyubiquitination and degradation. We showed that the ubiquitin ligase function of CRL4AMBRA1 is required to disrupt the assembly and attenuate the ligase activity of human CRL5SOCS3 and HIV‐1 CRL5VIF complexes as AMBRA1 depletion leads to hyperactivation of both CRL5 complexes. Moreover, CRL4AMBRA1 modulates interleukin‐6/STAT3 signaling and HIV‐1 infectivity that are regulated by CRL5SOCS3 and CRL5VIF, respectively. Thus, by discovering a substrate of CRL4AMBRA1, ELOC, the shared adapter of CRL5 ubiquitin ligases, we uncovered a novel CRL cross‐regulation pathway.

Synopsis

Embedded Image

The ubiquitin E3 ligase CRL4AMBRA1 targets Elongin C (ELOC), the shared adapter of CRL5 ubiquitin ligases, for polyubiquitination and degradation, thereby modulating IL‐6/STAT3 signaling and HIV‐1 infectivity that are regulated by CRL5SOCS3 and HIV‐1 CRL5VIF, respectively.

  • Quantitative proteomics identifies ELOC as a novel substrate of CRL4AMBRA1.

  • ELOC mediates the interaction between AMBRA1 and multiple CRL5 substrate receptors.

  • ELOC targeting by CRL4AMBRA1 attenuates the ligase activity of CRL5SOCS3 and HIV‐1 CRL5VIF.

  • CRL4AMBRA1 modulates CRL5SOCS3‐ and HIV‐1 CRL5VIF‐regulated functions.

  • AMBRA1
  • cullin‐RING ligase
  • HIV infection
  • interleukin‐6
  • ubiquitin

The EMBO Journal (2018) 37: e97508

  • Received June 5, 2017.
  • Revision received July 26, 2018.
  • Accepted August 1, 2018.
  • © 2018 The Authors
View Full Text

Subscribers, please sign in with your username and password.

Log in using your username and password

Enter your The EMBO Journal username.
Enter the password that accompanies your username.
Forgot your user name or password?

Log in through your institution

You may be able to gain access using your login credentials for your institution. Contact your library if you do not have a username and password.
If your organization uses OpenAthens, you can log in using your OpenAthens username and password. To check if your institution is supported, please see this list. Contact your library for more details.

Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$35.00

Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.

EMBO Members please login here to access the journals

Subscribe to the Journal

EMBO Journal

EMBO Reports

Recommend to your Librarian

EMBO Journal

EMBO Reports

 

 

Previous Article in this IssueNext Article in this Issue
Back to top

  • PDF
  • Share
  • Export
  • Print
Loading

PDF

Review Process

In this Issue
Volume 37, Issue 18
14 September 2018
The EMBO Journal: 37 (18)
About the cover
Alert me when this article is cited
Alert me if a correction is posted

Article

  • Article
    • Abstract
    • Synopsis
    • Introduction
    • Results
    • Discussion
    • Materials and Methods
    • Author contributions
    • Conflict of interest
    • Expanded View
    • Acknowledgements
    • References
  • Figures & Data
  • Transparent Process

Related Content

More Articles

  • NBS1 promotes the endonuclease activity of the MRE11‐RAD50 complex by sensing CtIP phosphorylation
    Roopesh Anand, Arti Jasrotia, Diana Bundschuh, Sean Michael Howard, Lepakshi Ranjha, Manuel Stucki, Petr Cejka
    The EMBO Journal : e101005
  • ABRO1 promotes NLRP3 inflammasome activation through regulation of NLRP3 deubiquitination
    Guangming Ren, Xuanyi Zhang, Yang Xiao, Wen Zhang, Yu Wang, Wenbing Ma, Xiaohan Wang, Pan Song, Lili Lai, Hui Chen, Yiqun Zhan, Jianhong Zhang, Miao Yu, Changhui Ge, Changyan Li, Ronghua Yin, Xiaoming Yang
    The EMBO Journal : e100376
  • Efficient mitotic checkpoint signaling depends on integrated activities of Bub1 and the RZZ complex
    Gang Zhang, Thomas Kruse, Claudia Guasch Boldú, Dimitriya H Garvanska, Fabian Coscia, Matthias Mann, Marin Barisic, Jakob Nilsson
    The EMBO Journal : e100977
More Article

Related Articles

Cited By...

Request Permissions

Subject Areas

  • Autophagy & Cell Death
  • Post-translational Modifications, Proteolysis & Proteomics
  • Systems & Computational Biology

Journal

  • Latest Online
  • Current Issue
  • Archive
  • Bibliometrics
  • E-Mail Editorial Office
  • Privacy Policy

Authors & Referees

  • Aims & Scope
  • Editors & Board
  • Transparent Process
  • Author Guidelines
  • Referee Guidelines
  • Open Access
  • Submit

Info

  • Alerts
  • RSS Feeds
  • Subscriptions & Access
  • Reprints & Permissions
  • Advertise & Sponsor
  • News & Press
  • Recommend to Librarian
  • Customer Service

EMBO

  • Funding & Awards
  • Events
  • Science Policy
  • Members
  • About EMBO

Online ISSN  1460-2075

Copyright© 2019 EMBO

This website is best viewed using the latest versions of all modern web browsers. Older browsers may not display correctly.