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

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

  • Elife. 2015 Dec 23;4:e11306. doi: 10.7554/eLife.11306.
David Tse Shen Lin 1 2 Elizabeth Conibear 1 2
Affiliations

Affiliations

  • 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.

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