PIASproteiner

PIASproteiner are a family of nuclear proteins that act as regulators of transcription factors, signal transduction pathways and protein stability. The name derives from the ability of the first discovered member, PIAS1, to inhibit activated STAT (Signal Transducer and Activator of Transcription) proteins. The family is conserved in eukaryotes and includes four paralogues in mammals: PIAS1, PIAS3, PIAS4 (also called PIAS2), and PIASX, which differ mainly in their C‑terminal SUMO E3 ligase domain and in their target specificity.

All PIAS proteins contain an N‑terminal SAP (SAF-A/B, Acinus, PIAS) domain, a proline-rich region, and a C‑terminal SP-RING (small cysteine‑rich region) domain that confers E3 SUMO ligase activity. The proteins shuttle between the cytoplasm and nucleus, and their localization is often controlled by post‑translational modifications. By catalyzing the transfer of small ubiquitin‑like modifier (SUMO) to target proteins, PIAS proteins modulate DNA binding, protein–protein interactions, subcellular trafficking, and degradation.

PIAS1, for example, SUMOylates STAT1, NF‑κB, p53, and p300, thereby attenuating inflammatory responses and DNA‑damage signaling. PIAS3 preferentially targets STAT3, antagonizing its oncogenic activity. PIAS4/2 can SUMOylate histone proteins and transcriptional co‑activators, influencing chromatin structure and gene expression. Mutations or dysregulation of PIAS proteins have been implicated in cancer, neurodegenerative diseases, and developmental disorders.

The functions of the PIAS family are studied using techniques such as co‑immunoprecipitation, chromatin immunoprecipitation, and mass spectrometry‑based proteomics. Their central role in controlling SUMO‑dependent signaling makes them attractive targets for therapeutic intervention.