fig2

Figure 2. Negative feedback mechanisms modulating genotoxic NF-κB activation. Upon genotoxic NF-κB activation, desumoylation enzyme SENP2 can be transcriptionally upregulated, which in turn decreases NEMO sumoylation and suppresses genotoxic NF-κB signaling. Similarly, MCPIP1 can be upregulated by NF-κB in response to genotoxic treatment. MCPIP1 may decrease NEMO linear ubiquitination and ELKS K63 polyubiquitination by facilitating their interaction with USP10. Meanwhile, MCPIP1/USP10 forms a complex with TANK, which bridges the association of the deubiquitinase complex with TRAF6 and suppresses TRAF6 ubiquitination. All these deubiquitination events could contribute to the abrogation of genotoxic NF-κB activation. In addition, as a canonical NF-κB target gene, IκBα induction could also diminish NF-κB activation by DNA damage. NF-κB: nuclear factor kappa B; SENP2: Sentrin/SUMO-specific protease 2; MCPIP1: monocyte chemotactic protein-1-induced protein-1; TANK: TRAF family member-associated NF-κB activator; TRAF6: TNF receptor-associated factor 6