title: Fas palmitoylation by the palmitoyl acyltransferase DHHC7 regulates Fas stability.
abstract: The death receptor Fas undergoes a variety of post-translational modifications including S-palmitoylation. This protein acylation has been reported essential for an optimal cell death signaling by allowing both a proper Fas localization in cholesterol and sphingolipid-enriched membrane nanodomains, as well as Fas high-molecular weight complexes. In human, S-palmitoylation is controlled by 23 members of the DHHC family through their palmitoyl acyltransferase activity. In order to better understand the role of this post-translational modification in the regulation of the Fas-mediated apoptosis pathway, we performed a screen that allowed the identification of DHHC7 as a Fas-palmitoylating enzyme. Indeed, modifying DHHC7 expression by specific silencing or overexpression, respectively, reduces or enhances Fas palmitoylation and DHHC7 co-immunoprecipitates with Fas. At a functional level, DHHC7-mediated palmitoylation of Fas allows a proper Fas expression level by preventing its degradation through the lysosomes. Indeed, the decrease of Fas expression obtained upon loss of Fas palmitoylation can be restored by inhibiting the lysosomal degradation pathway. We describe the modification of Fas by palmitoylation as a novel mechanism for the regulation of Fas expression through its ability to circumvent its degradation by lysosomal proteolysis.
authors.affiliation: Université de Nice, Institut de Biologie Valrose, CNRS UMR 7277, INSERM UMR 1091, Nice, France.
authors.forename: A
authors.initials: A
authors.lastname: Rossin
authors.affiliation: Université de Nice, Institut de Biologie Valrose, CNRS UMR 7277, INSERM UMR 1091, Nice, France.
authors.forename: J
authors.identifier: 0000000282282915
authors.initials: J
authors.lastname: Durivault
authors.affiliation: Université de Nice, Institut de Biologie Valrose, CNRS UMR 7277, INSERM UMR 1091, Nice, France.
authors.forename: T
authors.initials: T
authors.lastname: Chakhtoura-Feghali
authors.affiliation: Université de Nice, Institut de Biologie Valrose, CNRS UMR 7277, INSERM UMR 1091, Nice, France.
authors.forename: N
authors.initials: N
authors.lastname: Lounnas
authors.affiliation: Université de Nice, Institut de Biologie Valrose, CNRS UMR 7277, INSERM UMR 1091, Nice, France.
authors.forename: L
authors.initials: L
authors.lastname: Gagnoux-Palacios
authors.affiliation: Université de Nice, Institut de Biologie Valrose, CNRS UMR 7277, INSERM UMR 1091, Nice, France.
authors.forename: A-O
authors.initials: AO
authors.lastname: Hueber
mesh_terms: D000123:Acetyltransferases; D019943:Amino Acid Substitution; D017209:Apoptosis; D045744:Cell Line, Tumor; D003513:Cycloheximide / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054878:Lipoylation; D008247:Lysosomes / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D055550:Protein Stability / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
chemical_list: C491901:FAS protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011500:Protein Synthesis Inhibitors; D034741:RNA, Small Interfering; D019014:fas Receptor; D003513:Cycloheximide; D000123:Acetyltransferases; C447819:ZDHHC7 protein, human