ABHD17 proteins are novel protein depalmitoylases that regulate N-Ras palmitate turnover and subcellular localization
Open Access
- 23 December 2015
- journal article
- research article
- Published by eLife Sciences Publications, Ltd in eLife
- Vol. 4, e11306
- https://doi.org/10.7554/elife.11306
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.Keywords
Funding Information
- Canadian Institutes of Health Research (Institute of Genetics Team Grant, GPG-202165)
- Canada Foundation for Innovation (Leading Edge Fund, 30636)
- University of British Columbia (Four Year Fellowship (FYF))
- Canadian Institutes of Health Research (New Investigator Salary Award)
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