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
Reviewing Editor
- Philip A Cole, Johns Hopkins University, United States
Publication history
- Received: September 3, 2015
- Accepted: December 21, 2015
- Accepted Manuscript published: December 23, 2015 (version 1)
- 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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