PIAS3

E3 SUMO-protein ligase PIAS3 is an enzyme that in humans is encoded by the PIAS3 gene. PIAS proteins were originally identified in studies that were aimed to decipher the Janus Kinase (JAK)/STAT signaling pathway. The mammalian PIAS family consists of four members: PIAS1, PIAS2, PIAS3 and PIAS4. In Drosophila, a single PIAS homologue named dPIAS/Zimp has been identified. In yeast, two PIAS-related proteins were identified namely SIZ1 and SIZ2. Studies by different research groups have now identified a rapidly growing list of more than 60 proteins, most of them transcription factors that can be either positively or negatively regulated by members of the PIAS family through multiple mechanisms. Originally, PIAS3 was found to interact specifically with phosphorylated STAT3 in Interleukin -6 (IL-6) activated murine myeloblast M1 cells. This interaction is mediated via PIAS3 binding to the STAT3 DNA binding domain. Hence, STAT3 transcriptional activity is inhibited by the physical prevention of its binding to target genes. Subsequently, PIAS3 was also found to be a regulator protein of other key transcription factors, including MITF,NFκB,SMAD and estrogen receptor.