PARG inhibition suppresses breast cancer progression and potentiates immunoresponse through MTDH degradation mediated by E3 ligase ITCH-dependent ubiquitination.

ABSTRACT: PARG plays an important role in cancer progression and immunoresponse, but its role in breast cancer is not yet fully elucidated. The advanced breast cancer is still a persistent challenge in clinical oncology. Despite the encouraging progress made in cancer immunotherapy, its efficacy is still limited by tumor malignancy and the immunosuppressive microenvironment. Through comprehensive proteomic analysis employing liquid chromatography-tandem mass spectrometry, we identified ITCH-a HECT-family E3 ubiquitin ligase-as a novel interaction partner of PARG. Co-immunoprecipitation and ubiquitination assays revealed that the PARG inhibition markedly enhances the PARylation of the E3 ubiquitin ligase ITCH. This triggers its autoubiquitination-dependent activation, after which activated ITCH catal

SUBMITTER: Wang J 

PROVIDER: S-EPMC12714780 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature