E3 SUMO-protein ligase PIAS3 (PIAS3)

E3 SUMO-protein ligase PIAS3 (PIAS3) is a multifunctional regulatory protein primarily acting as an endogenous inhibitor of activated STAT3, a key transcription factor involved in mediating cytokine signaling and oncogenic processes[1][2][5]. PIAS3 blocks STAT3 transcriptional activity by direct binding and also possesses SUMO E3 ligase activity, adding SUMO (small ubiquitin-like modifier) proteins to nuclear substrates to alter their stability, localization, and function[1][2][5]. As a transcriptional co-regulator, PIAS3 modulates the activities of various other transcription factors—including NF-κB, Smad3, and steroid hormone receptors—either repressing or enhancing their transcriptional outputs[1][2][3][5]. Through these activities, PIAS3 plays critical roles in regulating immune responses, cell proliferation, apoptosis, and cellular homeostasis. PIAS3 deregulation has been associated with various human diseases, particularly cancer, making it a relevant target for research in oncology and immune modulation[2][6]. **Note:** There are currently no known approved drugs that specifically target PIAS3, nor validated clinical biomarkers for its targeting or pharmacodynamic monitoring. Its complex involvement in essential transcriptional and signaling pathways also raises safety concerns for direct therapeutic interventions.

Other names

Protein inhibitor of activated STAT 3PIAS3E3 SUMO-protein transferase PIAS3Protein inhibitor of activated STAT protein 3FLJ14651ZMIZ5zinc finger MIZ-type containing 5

Inhibition of STAT3 activation (by direct binding and blocking DNA-binding and transcriptional activity); Modulation of transcription factors via SUMOylation (covalent attachment of SUMO to target proteins); Regulation (both inhibition and activation) of other pathways such as NF-κB, TGF-β/Smad, and steroid hormone receptor activities