Figures & data
Figure 1. The COP9 signalosome (CSN) is a regulator of multiple oncogenic E3-ligases. CSN6 is activated by inputs from activated PI3K kinase pathway, as observed in breast cancers with HER2 amplification. CSN6 controls the activities of the E3 ligases COP1, MDM2 and SKP2. Through COP1, CSN mediates 14–3-3σ degradation, thereby relieving negative regulation of AKT, which, in turn, forms a positive feedback to activate CSN6. By activating MDM2 and SKP2 activity toward their tumor suppressor substrates p53 and p57kip2, respectively, CSN is hypothesized to promote oncogenesis.
