Regulation of gene-activation pathways by PIAS proteins in the immune system

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Abstract
Protein inhibitor of activated STAT (signal transducer and activator of transcription protein) proteins (PIAS proteins) regulate the activity of certain transcription factors — such as STATs, nuclear factor-κB and SMADs (SMA (small body size)- and MAD (mothers against decapentaplegic)-related proteins) — in cytokine-mediated signalling, using distinct mechanisms. PIAS proteins can inhibit transcription by blocking the DNA-binding activity of transcription factors. PIAS proteins can negatively or positively regulate transcription by recruiting transcriptional co-regulators, such as histone deacetylases, or p300 or CBP (cyclic-AMP-responsive-element-binding protein (CREB)-binding protein), respectively. PIAS proteins have SUMO (small ubiquitin-like modifier)-E3-ligase activity, which might be involved in transcriptional regulation. PIAS1 has specific effects on cytokine-mediated signalling by selectively regulating a subset of interferon- or tumour-necrosis-factor-responsive genes. PIAS1 is important in innate immunity. A deficiency in PIAS1 results in increased protection against viral and bacterial infection.