Attenuating ABHD17 isoforms augments the <i>S</i>-acylation and function of NOD2 and a subset of Crohn's disease-associated NOD2 variants.

ABSTRACT:

Background and aims

NOD2 is an intracellular innate immune receptor that detects bacterial peptidoglycan fragments. Although nominally soluble, some NOD2 is associated with the plasma membrane and endosomal compartments for microbial surveillance. This membrane targeting is achieved through post-translational S-acylation of NOD2 by the protein acyltransferase ZDHHC5. Membrane attachment is necessary to initiate a signaling cascade in response to cytosolic peptidoglycan fragments. Ultimately, this signaling results in the production of antimicrobial peptides and pro-inflammatory cytokines. In most cases, S-acylation is a reversible post-translational modification with removal of the fatty acyl chain catalyzed by one of several acyl protein thioesterases. Deacylation of

SUBMITTER: Dixon CL 

PROVIDER: S-EPMC10769251 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature