XAF1 antagonizes TRIM28 activity through the assembly of a ZNF313-mediated destruction complex to suppress tumor malignancy.

ABSTRACT: X-linked inhibitor of apoptosis-associated factor 1 (XAF1) is a stress-inducible pro-apoptotic protein that is commonly inactivated in multiple human cancers. Nevertheless, the molecular basis for its tumor suppression function remains largely uncharacterized. Here we report that XAF1 antagonizes the oncogenic activity of tripartite motif containing 28 (TRIM28) ubiquitin E3 ligase through zinc finger protein 313 (ZNF313)-induced ubiquitination and proteasomal degradation. XAF1 exerts apoptosis-promoting effect more strongly in TRIM28^+/+ versus XAF1^-/- tumor cells and suppresses tumor cell growth, migration, invasion, and epithelial-to-mesenchymal transition and xenograft tumor growth in a highly TRIM28-dependent fashion. Mechanistically, XAF1 interacts directly with t

SUBMITTER: Jang SH 

PROVIDER: S-EPMC11557793 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature