Fatty acids and cancer-amplified ZDHHC19 promote STAT3 activation through S-palmitoylation.

ABSTRACT: Signal transducer and activator of transcription 3 (STAT3) has a critical role in regulating cell fate, inflammation and immunity^1,2. Cytokines and growth factors activate STAT3 through kinase-mediated tyrosine phosphorylation and dimerization^3,4. It remains unknown whether other factors promote STAT3 activation through different mechanisms. Here we show that STAT3 is post-translationally S-palmitoylated at the SRC homology 2 (SH2) domain, which promotes the dimerization and transcriptional activation of STAT3. Fatty acids can directly activate STAT3 by enhancing its palmitoylation, in synergy with cytokine stimulation. We further identified ZDHHC19 as a palmitoyl acyltransferase that regulates STAT3. Cytokine stimulation increases STAT3 palmitoylation by promoting th

SUBMITTER: Niu J 

PROVIDER: S-EPMC6728214 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature