Protein inhibitor of activated STAT 1 (PIAS1) (PIAS1)

Protein inhibitor of activated STAT 1 (PIAS1) is a multi-functional E3 SUMO-protein ligase that plays a pivotal role in the post-translational modification of proteins through sumoylation (UniProt: O75925). In the context of Parkinson's disease and other synucleinopathies, PIAS1 is a central component of the machinery responsible for the sumoylation of alpha-synuclein, a process that regulates the protein's aggregation propensity and cellular toxicity (PubMed: 21248169). Research has demonstrated that PIAS1-mediated sumoylation can alter the solubility of alpha-synuclein, potentially serving as a protective mechanism against the formation of insoluble fibrils (PubMed: 28122244). Beyond its interaction with alpha-synuclein, PIAS1 is involved in regulating the JAK/STAT signaling pathway, DNA damage repair, and the activity of various transcription factors like p53 and NF-kappaB (PubMed: 15561726). As a therapeutic target, modulating PIAS1 activity offers a potential avenue to enhance the clearance of pathogenic protein aggregates in neurodegenerative diseases. However, the broad substrate specificity of PIAS1 poses significant challenges for drug development, as non-specific modulation could lead to adverse effects on immune regulation and genome stability (PubMed: 23604028).

Other names

E3 SUMO-protein ligase PIAS1Gu-binding proteinGBPRNA helicase II-binding proteinDDX21-binding proteinProtein inhibitor of activated STAT protein 1

Modulation of E3 SUMO-protein ligase activity to regulate the sumoylation and subsequent aggregation or degradation of alpha-synuclein.