2. Academic Validation
  3. Identification and dynamics of the human ZDHHC16-ZDHHC6 palmitoylation cascade

Identification and dynamics of the human ZDHHC16-ZDHHC6 palmitoylation cascade

  • Elife. 2017 Aug 15;6:e27826. doi: 10.7554/eLife.27826.
Laurence Abrami # 1,  Tiziano Dallavilla # 1 2,  Patrick A Sandoz 1,  Mustafa Demir 1,  Béatrice Kunz 1,  Georgios Savoglidis 2,  Vassily Hatzimanikatis 2,  F Gisou van der Goot 1
Affiliations

Affiliations

  • 1 Global Health Institute, Faculty of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • 2 Laboratory of Computational Systems Biotechnology, Faculty of Basic Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • # Contributed equally.
PMID: 28826475 DOI: 10.7554/eLife.27826
Abstract

S-Palmitoylation is the only reversible post-translational lipid modification. Knowledge about the DHHC palmitoyltransferase family is still limited. Here we show that human ZDHHC6, which modifies key proteins of the endoplasmic reticulum, is controlled by an upstream palmitoyltransferase, ZDHHC16, revealing the first palmitoylation cascade. The combination of site specific mutagenesis of the three ZDHHC6 palmitoylation sites, experimental determination of kinetic parameters and data-driven mathematical modelling allowed us to obtain detailed information on the eight differentially palmitoylated ZDHHC6 species. We found that species rapidly interconvert through the action of ZDHHC16 and the Acyl Protein Thioesterase APT2, that each species varies in terms of turnover rate and activity, altogether allowing the cell to robustly tune its ZDHHC6 activity.

Keywords

Acyl protein thioesterase; DHHC; ERAD; cell biology; endoplasmic reticulum; human; mouse; palmitoylation; turnover.

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