3 research outputs found
Overexpression of COP9 signalosome subunits, CSN7A and CSN7B, exerts different effects on adipogenic differentiation
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