DNAJA2 deficiency activates cGAS-STING pathway via the induction of aberrant mitosis and chromosome instability.

ABSTRACT: Molecular chaperone HSP70s are attractive targets for cancer therapy, but their substrate broadness and functional non-specificity have limited their role in therapeutical success. Functioning as HSP70's cochaperones, HSP40s determine the client specificity of HSP70s, and could be better targets for cancer therapy. Here we show that tumors defective in HSP40 member DNAJA2 are benefitted from immune-checkpoint blockade (ICB) therapy. Mechanistically, DNAJA2 maintains centrosome homeostasis by timely degrading key centriolar satellite proteins PCM1 and CEP290 via HSC70 chaperone-mediated autophagy (CMA). Tumor cells depleted of DNAJA2 or CMA factor LAMP2A exhibit elevated levels of centriolar satellite proteins, which causes aberrant mitosis characterized by abnormal spindles, chromosome mis

SUBMITTER: Huang Y 

PROVIDER: S-EPMC10462666 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature