PIAS1
Description
The PIAS1 (protein inhibitor of activated STAT 1) is a protein-coding gene located on chromosome 15.
E3 SUMO-protein ligase PIAS1 is an enzyme that in humans is encoded by the PIAS1 gene. This gene encodes a member of the mammalian PIAS [protein inhibitor of activated STAT-1 (signal transducer and activator of transcription-1)] family. This member contains a putative zinc-binding motif and a highly acidic region. It inhibits STAT1-mediated gene activation and the DNA binding activity, binds to Gu protein/RNA helicase II/DEAD box polypeptide 21, and interacts with androgen receptor (AR). It functions in testis as a nuclear receptor transcriptional coregulator and may have a role in AR initiation and maintenance of spermatogenesis.
PIAS1 acts as an E3 SUMO ligase, facilitating the attachment of SUMO (small ubiquitin-like modifier) proteins to other proteins. This process is essential for regulating protein function and stability. PIAS1 also serves as a SUMO-tethering factor, helping to bring SUMO-modifying enzymes and their target proteins together. PIAS1 plays a key role in transcriptional regulation, influencing the activity of genes involved in various pathways, including the STAT pathway (signal transducer and activator of transcription), the p53 pathway (a tumor suppressor gene), and the steroid hormone signaling pathway. PIAS1 can bind to DNA, specifically to regions rich in adenine and thymine bases. Interestingly, PIAS1's impact on gene expression can be either activation or silencing, depending on the specific context. PIAS1 can directly modify PML (promyelocytic leukemia protein), a protein involved in various cellular functions, by attaching SUMO to it. This modification ultimately leads to the breakdown of PML through the ubiquitin pathway. PIAS1 further enhances the SUMOylation of MTA1 (metastasis-associated protein 1), which plays a role in cancer progression. PIAS1 also contributes to the regulation of adipogenesis (fat cell formation) by promoting the SUMOylation and subsequent degradation of CEBPB (CCAAT/enhancer-binding protein beta), a transcription factor involved in fat cell development. PIAS1 influences the movement and location of MSX1 (muscle segment homeobox 1), a protein involved in muscle development, within the nucleus. This movement brings MSX1 closer to its target genes, allowing for their regulation. PIAS1 is also required for MSX1 to bind to specific regions of target gene promoters, independent of its SUMOylation activity. It can also bind to a specific sequence in the MYOD1 (myogenic differentiation 1) gene promoter, which is involved in muscle cell development.
PIAS1 is also known as DDXBP1, GBP, GU/RH-II, ZMIZ3.
