COP9 signalosome complex subunit 1

COP9 signalosome complex subunit 1 (GPS1, also called SGN1) is an essential component of the COP9 signalosome complex (CSN), a multi-subunit regulatory complex involved in ubiquitin-dependent protein degradation and cell signaling (UniProt: Q13098). The CSN mediates deneddylation of cullin subunits in SCF-type E3 ligase complexes, thereby regulating their ubiquitin ligase activity. The complex also participates in phosphorylation of key regulatory proteins including p53, c-jun, and IκBα, potentially through associated kinases CK2 and PKD.

GPS1 is widely expressed and functions as a central regulator of protein quality control and signal transduction pathways. Its role in ubiquitin-mediated proteolysis links it to cellular homeostasis and developmental processes governed by targeted protein degradation.

GPS1 is downregulated in Alzheimer's Disease brain tissue (Chaparral AD proteomics). Quantitative proteomics of post-mortem AD brain compared to age-matched controls detected reduced GPS1 levels with a mean log2 fold-change of −0.63 across subcellular fractions. This reduction in CSN activity may impair ubiquitin-dependent proteolytic pathways implicated in AD pathogenesis, potentially contributing to altered protein homeostasis characteristic of the disease.