1. Biochemistry and Chemical Biology
  2. Cell Biology

A shunt pathway limits the CaaX processing of Hsp40 Ydj1p and regulates Ydj1p-dependent phenotypes

  1. Emily R Hildebrandt
  2. Michael Cheng
  3. Peng Zhao
  4. June H Kim
  5. Lance Wells
  6. Walter K Schmidt  Is a corresponding author
  1. University of Georgia, United States
https://doi.org/10.7554/eLife.15899
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  1. Emily R Hildebrandt
  2. Michael Cheng
  3. Peng Zhao
  4. June H Kim
  5. Lance Wells
  6. Walter K Schmidt
(2016)
A shunt pathway limits the CaaX processing of Hsp40 Ydj1p and regulates Ydj1p-dependent phenotypes
eLife 5:e15899.
https://doi.org/10.7554/eLife.15899
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Abstract

The modifications occurring to CaaX proteins have largely been established using few reporter molecules (e.g. Ras, yeast a-factor mating pheromone). These proteins undergo three coordinated COOH-terminal events: isoprenylation of the cysteine, proteolytic removal of aaX, and COOH-terminal methylation. Here, we investigated the coupling of these modifications in the context of the yeast Ydj1p chaperone. We provide genetic, biochemical, and biophysical evidence that the Ydj1p CaaX motif is isoprenylated but not cleaved and carboxylmethylated. Moreover, we demonstrate that Ydj1p-dependent thermotolerance and Ydj1p localization are perturbed when alternative CaaX motifs are transplanted onto Ydj1p. The abnormal phenotypes revert to normal when post-isoprenylation events are genetically interrupted. Our findings indicate that proper Ydj1p function requires an isoprenylatable CaaX motif that is resistant to post-isoprenylation events. These results expand on the complexity of protein isoprenylation and highlight the impact of post-isoprenylation events in regulating the function of Ydj1p and perhaps other CaaX proteins.

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Author details

  1. Emily R Hildebrandt

    Department of Biochemistry and Molecular Biology, University of Georgia, Athens, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Michael Cheng

    Department of Biochemistry and Molecular Biology, University of Georgia, Athens, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Peng Zhao

    Department of Biochemistry and Molecular Biology, University of Georgia, Athens, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. June H Kim

    Department of Biochemistry and Molecular Biology, University of Georgia, Athens, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Lance Wells

    Complex Carbohydrate Research Center, University of Georgia, Athens, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4956-5363

  6. Walter K Schmidt

    Biochemistry and Molecular Biology, University of Georgia, Athens, United States
    For correspondence
    wschmidt@bmb.uga.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3359-3434

Funding

National Institute of General Medical Sciences (P41GM103490)

  • Lance Wells

University of Georgia

  • Walter K. Schmidt

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

Copyright

© 2016, Hildebrandt 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. Emily R Hildebrandt
  2. Michael Cheng
  3. Peng Zhao
  4. June H Kim
  5. Lance Wells
  6. Walter K Schmidt
(2016)
A shunt pathway limits the CaaX processing of Hsp40 Ydj1p and regulates Ydj1p-dependent phenotypes
eLife 5:e15899.
https://doi.org/10.7554/eLife.15899

Share this article

https://doi.org/10.7554/eLife.15899

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