PIAS1 (Protein Inhibitor of Activated STAT1) is a protein that belongs to the PIAS (Protein Inhibitors of Activated STAT) family. PIAS1 was initially identified as an inhibitor of STAT1, where it interacts with activated STAT1 to form a complex. This interaction prevents STAT1 dimers from binding to DNA by masking their functional domains, thereby inhibiting transcription. In transcriptional regulation, PIAS1 exerts inhibitory effects on transcription factors such as STAT1 and NF-κB by blocking their DNA-binding capabilities without relying on its own SUMOylation or the SUMO E3 ligase activity of PIAS. PIAS1 also interacts with non-transcription factors, such as focal adhesion kinase (FAK), leading to the SUMOylation of FAK, which results in its autophosphorylation. PIAS1 interacts with the tumor suppressor protein p73, a member of the p53 family, leading to the SUMO modification of p73 and inhibiting its transcriptional activity. This interaction decreases the expression of p21, resulting in a reduced proportion of cells in the G1 phase and promoting cell cycle progression. The expression of PIAS1 is significantly associated with the differentiation status of tumor cells in hepatocellular carcinoma and colorectal cancer, where lower expression correlates with poorer differentiation.
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