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Ubiquitin turnover and endocytic trafficking in yeast are regulated by Ser57 phosphorylation of ubiquitin

  1. Sora Lee
  2. Jessica M Tumolo
  3. Aaron C Ehlinger
  4. Kristin K Jernigan
  5. Susan J Qualls-Histed
  6. Pi-Chiang Hsu
  7. W Hayes McDonald
  8. Walter J Chazin
  9. Jason A MacGurn  Is a corresponding author
  1. Vanderbilt University, United States
  2. Cornell University, United States
Research Article
  • Cited 2
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Cite this article as: eLife 2017;6:e29176 doi: 10.7554/eLife.29176

Abstract

Despite its central role in protein degradation little is known about the molecular mechanisms that sense, maintain, and regulate steady state concentration of ubiquitin in the cell. Here, we describe a novel mechanism for regulation of ubiquitin homeostasis that is mediated by phosphorylation of ubiquitin at the Ser57 position. We find that loss of Ppz phosphatase activity leads to defects in ubiquitin homeostasis that are at least partially attributable to elevated levels of Ser57 phosphorylated ubiquitin. Phosphomimetic mutation at the Ser57 position of ubiquitin conferred increased rates of endocytic trafficking and ubiquitin turnover. These phenotypes are associated with bypass of recognition by endosome-localized deubiquitylases - including Doa4 which is critical for regulation of ubiquitin recycling. Thus, ubiquitin homeostasis is significantly impacted by the rate of ubiquitin flux through the endocytic pathway and by signaling pathways that converge on ubiquitin itself to determine whether it is recycled or degraded in the vacuole.

Article and author information

Author details

  1. Sora Lee

    Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Jessica M Tumolo

    Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Aaron C Ehlinger

    Department of Biochemistry, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Kristin K Jernigan

    Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Susan J Qualls-Histed

    Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Pi-Chiang Hsu

    Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. W Hayes McDonald

    Department of Biochemistry, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Walter J Chazin

    Department of Biochemistry, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Jason A MacGurn

    Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States
    For correspondence
    jason.a.macgurn@vanderbilt.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5063-259X

Funding

National Institute of General Medical Sciences (R00 GM101077)

  • Jason A MacGurn

National Institute of General Medical Sciences (R01 GM118491)

  • Jason A MacGurn

American Federation for Aging Research (Research Grants for Junior Faculty)

  • Jason A MacGurn

National Institute of General Medical Sciences (R35 GM118089)

  • Walter J Chazin

National Heart, Lung, and Blood Institute (T32 HL069765)

  • Sora Lee

National Cancer Institute (T32 CA119925)

  • Jessica M Tumolo

National Cancer Institute (T32 CA009582)

  • Aaron C Ehlinger

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

Reviewing Editor

  1. Wade Harper, Harvard Medical School, United States

Publication history

  1. Received: May 31, 2017
  2. Accepted: November 10, 2017
  3. Accepted Manuscript published: November 13, 2017 (version 1)
  4. Version of Record published: November 29, 2017 (version 2)

Copyright

© 2017, Lee 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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