The COP9 Signalosome Subunit 7A (COPS7A) is a crucial component of the COP9 signalosome (CSN) complex, which is an evolutionarily conserved multi-subunit protease. This complex plays a significant role in regulating the activity of the ubiquitin conjugation pathway, which is essential for various cellular processes, including protein degradation, cell cycle control, and signal transduction .
The COP9 signalosome complex is composed of several subunits, including CSN1 (COPS1), CSN2 (COPS2), CSN3 (COPS3), CSN4 (COPS4), CSN5 (COPS5), CSN6 (COPS6), CSN7A (COPS7A), and CSN8 (COPS8). The CSN7A subunit contains a PCI (Proteasome CSN9 initiation factor 3) region and a coiled-coil region, which are crucial for its interaction with other subunits of the complex .
The primary function of the COP9 signalosome is to regulate the ubiquitin conjugation pathway by mediating the deneddylation of SCF-type E3 ligase complexes. This deneddylation process leads to a decrease in the ubiquitin ligase activity of SCF-complexes, thereby controlling the degradation of various proteins . Additionally, the COP9 signalosome is involved in the phosphorylation of several key proteins, including p53, c-Jun, IκB-α, and IRF-8. The phosphorylation of these proteins by the CSN complex protects them from degradation by the ubiquitin-proteasome system .
Mutations or dysregulation of the COP9 signalosome subunits, including COPS7A, have been associated with several diseases and developmental disorders. For instance, alterations in the CSN complex can lead to defects in cell cycle control and signal transduction, contributing to the development of cancer and other proliferative diseases .