Identification of ubiquitin Ser57 kinases regulating the oxidative stress response in yeast

Abstract

Ubiquitination regulates many different cellular processes, including protein quality control, membrane trafficking, and stress responses. The diversity of ubiquitin functions in the cell is partly due to its ability to form chains with distinct linkages that can alter the fate of substrate proteins in unique ways. The complexity of the ubiquitin code is further enhanced by post-translational modifications on ubiquitin itself, the biological functions of which are not well understood. Here, we present genetic and biochemical evidence that serine 57 (Ser57) phosphorylation of ubiquitin functions in stress responses in Saccharomyces cerevisiae, including the oxidative stress response. We also identify and characterize the first known Ser57 ubiquitin kinases in yeast and human cells, and we report that two Ser57 ubiquitin kinases regulate the oxidative stress response in yeast. These studies implicate ubiquitin phosphorylation at the Ser57 position as an important modifier of ubiquitin function, particularly in response to proteotoxic stress.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Nathaniel L Hepowit

    Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Kevin N Pereira

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

    Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Walter J Chazin

    Biochemistry, Chemistry, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2180-0790
  5. 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 Institutes of Health (R21 AG053562)

  • Jason A MacGurn

National Institutes of Health (R01 GM118491)

  • Jason A MacGurn

National Institutes of Health (R35 GM118089)

  • Walter J Chazin

National Institutes of Health (T32 CA119925)

  • Jessica M Tumolo

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

Reviewing Editor

  1. Benoît Kornmann, University of Oxford, United Kingdom

Publication history

  1. Received: April 22, 2020
  2. Accepted: October 18, 2020
  3. Accepted Manuscript published: October 19, 2020 (version 1)
  4. Version of Record published: November 6, 2020 (version 2)

Copyright

© 2020, Hepowit 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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  1. Nathaniel L Hepowit
  2. Kevin N Pereira
  3. Jessica M Tumolo
  4. Walter J Chazin
  5. Jason A MacGurn
(2020)
Identification of ubiquitin Ser57 kinases regulating the oxidative stress response in yeast
eLife 9:e58155.
https://doi.org/10.7554/eLife.58155

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