E3 SUMO-protein ligase PIAS2 (PIAS2)

E3 SUMO-protein ligase PIAS2 (PIAS2), also known as protein inhibitor of activated STAT2, is a member of the PIAS protein family and functions as an E3-type small ubiquitin-like modifier (SUMO) ligase. Its primary role is as a transcriptional co-regulator, mediating SUMOylation of a wide range of transcription factors including STATs, p53, NF-κB, SMADs, and others. PIAS2 modulates cellular gene expression through both activation and repression, impacting numerous biological processes such as immune response, cell cycle, and DNA repair. It plays a crucial role in cytokine signaling—particularly in the JAK/STAT pathway—and is implicated in diverse human diseases, especially cancer, immune and inflammatory disorders, and dementia. Multiple isoforms exist due to alternative splicing. PIAS2's broad regulatory functions make it a potential therapeutic target, although direct inhibitors are not currently clinically available[1][2][3].

Other names

PIAS2PIASXARIP3 (Androgen receptor-interacting protein 3)DIP (DAB2-interacting protein)Miz1 (Msx-interacting zinc finger protein)PIASX-betaPIASX-alphaZMIZ4SIZ2PIAS-NY proteinDAB2-interacting proteinE3 SUMO-protein transferase PIAS2

SUMOylation of transcription factors and coregulatory proteins, modulating their activity (e.g., inhibiting or activating gene expression through STAT or NF-κB pathways)[1][2][3]. Recruitment of histone deacetylases and other chromatin modifiers, leading to gene silencing[2]. Protein–protein interaction and relocalization of transcriptional regulators within the nucleus[3].