1. Cell Biology
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The complex of TRIP-Br1 and XIAP ubiquitinates and degrades multiple adenylyl cyclase isoforms

  1. Wenbao Hu
  2. Xiaojie Yu
  3. Zhengzhao Liu
  4. Ying Sun
  5. Xibing Chen
  6. Xin Yang
  7. Xiaofen Li
  8. Wai Kwan Lam
  9. Yuanyuan Duan
  10. Xu Cao
  11. Hermann Steller
  12. Kai Liu
  13. Pingbo Huang  Is a corresponding author
  1. Hong Kong University of Science and Technology, Hong Kong
  2. The Rockefeller University, United States
Research Article
  • Cited 9
  • Views 1,658
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Cite this article as: eLife 2017;6:e28021 doi: 10.7554/eLife.28021

Abstract

Adenylyl cyclases (ACs) generate cAMP, a second messenger of utmost importance that regulates a vast array of biological processes in all kingdoms of life. However, almost nothing is known about how AC activity is regulated through protein degradation mediated by ubiquitination or other mechanisms. Here, we show that transcriptional regulator interacting with the PHD-bromodomain 1(TRIP-Br1, Sertad1), a newly identified protein with poorly characterized functions, acts as an adaptor that bridges the interaction of multiple AC isoforms with X-linked inhibitor of apoptosis protein (XIAP), a RING-domain E3 ubiquitin ligase. XIAP ubiquitinates a highly conserved Lys residue in AC isoforms and thereby accelerates the endocytosis and degradation of multiple AC isoforms in human cell lines. And XIAP/TRIP-Br1-mediated degradation of ACs forms part of a negative-feedback loop that controls the homeostasis of cAMP signaling in mice. Our findings reveal a previously unrecognized mechanism for degrading multiple AC isoforms and modulating the homeostasis of cAMP signaling.

Article and author information

Author details

  1. Wenbao Hu

    Division of Life Science, Hong Kong University of Science and Technology, Kwoloon, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  2. Xiaojie Yu

    Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  3. Zhengzhao Liu

    Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  4. Ying Sun

    Division of Life Science, Hong Kong University of Science and Technology, Kowloo, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  5. Xibing Chen

    Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  6. Xin Yang

    Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  7. Xiaofen Li

    Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  8. Wai Kwan Lam

    Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  9. Yuanyuan Duan

    Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  10. Xu Cao

    Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  11. Hermann Steller

    Strang Laboratory of Apoptosis and Cancer Biology, Howard Hughes Medical Institute,, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Kai Liu

    Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  13. Pingbo Huang

    Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong
    For correspondence
    bohuangp@ust.hk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4560-8760

Funding

The Kong Kong Grants Council (GRF660913)

  • Pingbo Huang

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal procedures were approved by the University Committee on Research Practices at the Hong Kong University of Science and Technology (the ethics protocol number 2014028).

Reviewing Editor

  1. Volker Dötsch, J.W. Goethe-University, Germany

Publication history

  1. Received: April 22, 2017
  2. Accepted: June 28, 2017
  3. Accepted Manuscript published: June 28, 2017 (version 1)
  4. Version of Record published: July 10, 2017 (version 2)
  5. Version of Record updated: July 11, 2017 (version 3)

Copyright

© 2017, Hu et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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