COP9 signalosome complex subunit 5 (CSN5)

COP9 signalosome complex subunit 5 (CSN5), also known as JAB1, is a zinc-dependent metalloprotease and isopeptidase that forms the catalytic core of the COP9 signalosome (CSN), an evolutionarily conserved multi-protein complex involved in the regulation of ubiquitin-proteasome-mediated protein degradation via deneddylation of cullin-RING ubiquitin ligases[1][3][4][5][8]. CSN5 contains a signature Jab1/MPN/Mov34 (JAMM) motif that chelates metal ions and confers catalytic activity[1][7]. CSN5 plays a critical role in cell cycle progression, cell survival, and transcription regulation and is considered an oncogene due to its frequent overexpression in human cancers and association with poor prognosis[2]. In addition to its function within the CSN, CSN5 may also operate as a monomer or in smaller complexes and interacts with several key cell cycle and signaling proteins, including CDK2 and c-Jun[2]. Its biological and biochemical importance, essential roles in development, and implication as a cancer driver make it a significant therapeutic target, though safety concerns exist due to its essential cellular functions[2][4][7].

Other names

JAB1COPS5Jab1/CSN5c-Jun activation domain-binding protein-1Jab1CSN subunit 5

Inhibition of CSN5’s isopeptidase/deneddylase catalytic activity (primarily at the JAMM motif)[7]. Inhibition of protein deneddylation, leading to impaired function of cullin-RING ubiquitin ligases and altered protein degradation[7].