Format

Send to

Choose Destination
Elife. 2015 Dec 23;4:e11306. doi: 10.7554/eLife.11306.

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

Author information

1
Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada.
2
Department of Medical Genetics, University of British Columbia, Vancouver, Canada.

Abstract

Dynamic changes in protein S-palmitoylation are critical for regulating protein localization and signaling. 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 uncharacterized 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 that the family of depalmitoylation enzymes may be substantially broader than previously believed.

KEYWORDS:

ABHD17A; ABHD17B; ABHD17C; APT1; Acyl Protein Thioesterase; FAM108A1; FAM108B1; FAM108C1; N-Ras; PSD95; Palmostatin B; biochemistry; cell biology; depalmitoylation; human; palmitoylation

PMID:
26701913
PMCID:
PMC4755737
DOI:
10.7554/eLife.11306
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center