The COP9 signalosome (CSN) is an essential regulator of cullin-RING-ubiquitin (Ub) ligases (CRLs), which ubiquitinate important cellular regulators and target them for degradation by the Ub proteasome system (UPS). The CSN exhibits deneddylating activity localized on subunit CSN5, which removes the ubiquitin-like protein Nedd8 from the cullins of CRLs. CSN-mediated deneddylation is an important step in the process of CRL remodeling, in which new substrate recognition units are incorporated into Ub ligases to meet changed requirements for proteolysis in cells. For instance, extensive CRL remodeling occurs during adipogenic differentiation when new CRL3s are formed. Diversification of CSN complexes during evolution is most likely another adaptation to meet different cellular requirements. Best known CSN variants are formed by different CSN subunit isoforms. For instance, in plant cells, isoforms have been identified for the MPN-domain subunits CSN5 (CSN5A and CSN5B) and CSN6 (CSN6A and CSN6B) which form four distinct CSN variants. In mammalian cells CSNCSN7A and CSNCSN7B variants are generated by CSN7 isoforms. We demonstrate that the two variants coexist in human LiSa-2 cells and in mouse embryonic fibroblasts. During adipogenic differentiation of LiSa-2 cells CSN7B increases in parallel with an elevation of the total CSN complex. Permanent overexpression of Flag-CSN7B but not of Flag-CSN7A accelerates adipogenesis in LiSa-2 cells indicating a specific function of the CSNCSN7B variant in stimulating adipogenesis. Silencing of CSN7A as well as of CSN7B in LiSa-2 cells and in mouse embryonic fibroblasts (MEFs) reduces adipogenic differentiation demonstrating that both CSNCSN7A and CSNCSN7B variants are involved in the process.
Keywords: COP9 signalosome; CSN7A; CSN7B; LiSa‐2 cells; adipogenesis; mouse embryonic fibroblasts.