ABHD17 proteins are novel protein depalmitoylases that regulate N-Ras palmitate turnover and subcellular localization

  1. David Tse Shen Lin
  2. Elizabeth Conibear  Is a corresponding author
  1. University of British Columbia, Canada

Abstract

Dynamic changes in protein S-palmitoylation are critical for regulating protein localization and signalling. Only two enzymes - the acyl-protein thioesterases APT1 and APT2 - are known to catalyze palmitate removal from cytosolic cysteine residues. It is unclear if these enzymes act constitutively on all palmitoylated proteins, or if additional depalmitoylases exist. Using a dual pulse-chase strategy comparing palmitate and protein half-lives, we found knockdown or inhibition of APT1 and APT2 blocked depalmitoylation of Huntingtin, but did not affect palmitate turnover on postsynaptic density protein 95 (PSD95) or N-Ras. We used activity profiling to identify novel serine hydrolase targets of the APT1/2 inhibitor Palmostatin B, and discovered that a family of uncharacterised ABHD17 proteins can accelerate palmitate turnover on PSD95 and N-Ras. ABHD17 catalytic activity is required for N-Ras depalmitoylation and re-localization to internal cellular membranes. Our findings indicate the family of depalmitoylation enzymes may be substantially broader than previously believed.

Article and author information

Author details

  1. David Tse Shen Lin

    Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Elizabeth Conibear

    Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, Canada
    For correspondence
    conibear@cmmt.ubc.ca
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Philip A Cole, Johns Hopkins University, United States

Version history

  1. Received: September 3, 2015
  2. Accepted: December 21, 2015
  3. Accepted Manuscript published: December 23, 2015 (version 1)
  4. Version of Record published: February 1, 2016 (version 2)

Copyright

© 2015, Lin & Conibear

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. David Tse Shen Lin
  2. Elizabeth Conibear
(2015)
ABHD17 proteins are novel protein depalmitoylases that regulate N-Ras palmitate turnover and subcellular localization
eLife 4:e11306.
https://doi.org/10.7554/eLife.11306

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https://doi.org/10.7554/eLife.11306

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