Protein inhibitor of activated STAT 1 (PIAS1)

Protein inhibitor of activated STAT 1 (PIAS1) is a nuclear protein functioning as an E3 SUMO-protein ligase, transcriptional coregulator, and scaffold attachment factor. PIAS1 selectively interacts with and inhibits STAT1 after cytokine stimulation by blocking its DNA-binding and gene activation capacity, thus acting as a negative regulator of interferon and cytokine signaling pathways. PIAS1 can also modulate the activities of other transcription factors, such as the androgen receptor, p53, SMAD proteins, and NF-κB, by repressing or enhancing their transcriptional functions depending on cellular context. Its E3 ligase activity promotes the sumoylation of target proteins, regulating their localization and function. PIAS1 is important for maintaining immune homeostasis and preventing excessive inflammatory responses, and it has been implicated in cellular responses relevant to cancer, inflammation, and infection. No selective drugs target PIAS1 clinically, but it is of research interest given its central role in several signaling pathways.

Other names

E3 SUMO-protein ligase PIAS1DDXBP1Gu-binding protein (GBP)GU/RH-IIZMIZ3DEAD/H box-binding protein 1RNA helicase II-binding proteinZinc finger, MIZ-type containing 3AR interacting proteinE3 SUMO-protein transferase PIAS1Protein inhibitor of activated STAT protein 1

Drugs or molecules that hypothetically target PIAS1 would inhibit or modulate its SUMO ligase or transcriptional repressor activity, leading to increased STAT1 (and potentially p53) activity or altered cytokine responsiveness