PT  - JOURNAL ARTICLE
AU  - Laurence Abrami
AU  - Tiziano Dallavilla
AU  - Patrick A. Sandoz
AU  - Mustafa Demir
AU  - Béatrice Kunz
AU  - Georgios Savoglidis
AU  - Vassily Hatzimanikatis
AU  - F. Gisou van der Goot
TI  - Identification and dynamics of the DHHC16-DHHC6 palmitoylation cascade
AID  - 10.1101/134007
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 134007
4099  - http://biorxiv.org/content/early/2017/05/03/134007.short
4100  - http://biorxiv.org/content/early/2017/05/03/134007.full
AB  - S-Palmitoylation is the only reversible post-translational lipid modification. Knowledge about the DHHC family of palmitoyltransferases is very limited. Here we show that mammalian DHHC6, which modifies key proteins of the endoplasmic reticulum, is controlled by an upstream palmitoyltransferase, DHHC16, revealing the first palmitoylation cascade. Combination of site specific mutagenesis of the three DHHC6 palmitoylation sites, experimental determination of kinetic parameters and data-driven mathematical modelling allowed us to obtain detailed information on the 8 differentially palmitoylated DHHC6 species. We found that species rapidly interconvert through the action of DHHC16 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 DHHC6 activity.