Palmitoyltransferase ZDHHC3 Aggravates Nonalcoholic Steatohepatitis by Targeting S-Palmitoylated IRHOM2.

ABSTRACT: Underestimation of the complexity of pathogenesis in nonalcoholic steatohepatitis (NASH) significantly encumbers development of new drugs and targeted therapy strategies. Inactive rhomboid protein 2 (IRHOM2) has a multifunctional role in regulating inflammation, cell survival, and immunoreaction. Although cytokines and chemokines promote IRHOM2 trafficking or cooperate with partner factors by phosphorylation or ubiquitin ligases-mediated ubiquitination to perform physiological process, it remains unknown whether other regulators induce IRHOM2 activation via different mechanisms in NASH progression. Here the authors find that IRHOM2 is post-translationally S-palmitoylated at C476 in iRhom homology domain (IRHD), which facilitates its cytomembrane translocation and stabilization. Fatty-acids

SUBMITTER: Xu M 

PROVIDER: S-EPMC10558657 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature