Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in COP9 signalosome complex subunit 6
CSN6 (COP9 signalosome subunit 6; COP9 subunit 6; MOV34 homolog, 34 kD) is one of the eight subunits of COP9 signalosome, a highly conserved protein complex with diverse functions, including several important intracellular pathways such as the ubiquitin/proteasome system, DNA repair, cell cycle, developmental changes, and some aspects of immune responses. CSN6 is an MPN-domain protein that directly interacts with the MPN+-domain subunit CSN5. It is cleaved during apoptosis by activated caspases. CSN6 processing occurs in CSN/CRL (cullin-RING Ub ligase) complexes and is followed by the cleavage of Rbx1, the direct interaction partner of CSN6. CSN6 cleavage enhances CSN-mediated deneddylating activity (i.e. cleavage of ubiquitin-like protein Nedd8 (neural precursor cell expressed, developmentally downregulated 8)) in the cullin 1 in cells. The cleavage of Rbx1 and increased deneddylation of cullins inactivate CRLs and presumably stabilize pro-apoptotic factors for final apoptotic steps. While CSN6 shows a typical MPN metalloprotease fold, it lacks the canonical JAMM motif, and therefore does not show catalytic isopeptidase activity.