Protein inhibitor of activated STAT

Protein inhibitor of activated STAT (PIAS), also known as E3 SUMO-protein ligase PIAS, is a protein that regulates transcription in mammals. PIAS proteins act as transcriptional co-regulators with at least 60 different proteins in order to either activate or repress transcription. The transcription factors STAT, NF-κB, p73, and p53 are among the many proteins that PIAS interacts with.

The seven proteins that belong to the mammalian PIAS family are encoded by four genes: PIAS1, PIAS2 (PIASx), PIAS3, and PIAS4 (PIASy). Apart from PIAS1, each gene encodes two protein isoforms. Homologues of PIAS proteins have been found in other eukaryotes, including Zimp/dPIAS in Drosophila melanogaster and zfPIAS4a in zebrafish. SIZ1 and SIZ2 were two homologues identified in yeast.

PIAS proteins contain each conserved domain and motif of the PIAS protein family, with a few exceptions. The known functions of these domains and motifs are similar among all PIAS protein family members. These functions include acting as E3 SUMO-protein ligases during SUMOylation, which is an important process in transcriptional regulation. Presently, less is known about the higher order structure of PIAS proteins. The three-dimensional protein structures of PIAS2, PIAS3, and SIZ1 have only recently been solved.

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