Fig. 5.

CSNAP influences the strength of the CSN-CRL interaction. Diagram representing the CRL cycle. CRLs form dynamic complexes with various adaptors and substrate receptors. The conjunction of Nedd8 to a conserved lysine residue in the cullin subunit, induces a conformational change that activates the CRL complex, promoting ubiquitin transfer to the substrate. The CSN complex inactivates CRL assemblies by two independent mechanisms, catalytic and non-catalytic. The first involves catalytic removal of the Nedd8 conjugate, while the second is mediated through physical binding to CRLs, sterically precluding interactions with E2 enzymes and ubiquitination substrates. Subsequently, after CSN dissociation, CRLs can be disassembled and assembled into new configurations, or bind Cand1. This cycle enables CRL adaptation according to cellular need, enabling specific substrates to be ubiquitinated. Our results indicate that CSNAP reduces the affinity of CSN for CRL, thus enabling efficient disassembly and remodeling of CRL complexes. In the absence of CSNAP, the disassembly and assembly steps of the cycle are compromised, as designated by the red dashed lines, affecting the reconfiguration of CRL assemblies, and their ability to respond to cellular stimuli