The seventh zinc finger motif of A20 is required for the suppression of TNF-α-induced apoptosis

• The ZnF7 mutant of A20 failed to suppress TNF-α-induced apoptosis.
• In the absence of cIAP1/2, A20 did not suppress TNF-α-induced apoptosis.
• A20 was suggested to suppress TNF-α-induced apoptosis through controlling cIAP1/2.

The ubiquitin-editing enzyme A20 suppresses nuclear factor-κB (NF-κB) activation and tumor necrosis factor-α (TNF-α)-induced apoptosis in a deubiquitinating and ubiquitin ligase activity-dependent manner. Although recent studies revealed that A20 regulates NF-κB independently of its enzymatic activity through its seventh zinc finger motif (ZnF7), the involvement of ZnF7 in TNF-α-induced apoptosis is not clear. In this study, ZnF7 was found to be important for A20-mediated suppression of TNF-α-induced apoptosis. We also found that the ubiquitin ligases cIAP1/2 are required for A20 to suppress TNF-α-induced apoptosis. Because A20 binds to cIAP1/2 through ZnF7, these results suggest that A20 may control cIAP1/2 when suppressing TNF-α-induced apoptosis.