Identification and dynamics of the human ZDHHC 16-ZDHHC6 palmitoylation cascade

被引：94

作者：

Abrami, Laurence ^{[1
]}

Dallavilla, Tiziano ^{[1
,2
]}

Sandoz, Patrick A. ^{[1
]}

Demir, Mustafa ^{[1
]}

Kunz, Beatrice ^{[1
]}

Savoglidis, Georgios ^{[2
]}

Hatzimanikatis, Vassily ^{[2
]}

van der Goot, F. Gisou ^{[1
]}

机构：

[1] Ecole Polytech Fed Lausanne, Fac Life Sci, Global Hlth Inst, Lausanne, Switzerland

[2] Ecole Polytech Fed Lausanne, Fac Basic Sci, Lab Computat Syst Biotechnol, Lausanne, Switzerland

来源：

ELIFE | 2017年 / 6卷

基金：

欧洲研究理事会;

关键词：

STEADY-STATE APPROXIMATION; PROTEIN PALMITOYLATION; S-PALMITOYLATION; REQUIRES PALMITOYLATION; TRAFFICKING; INHIBITION;

D O I：

10.7554/eLife.27826

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：24

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