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

The ubiquitin-editing enzyme A20 suppresses nuclear factor-kappa B (NF-kappa B) activation and tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis in a deubiquitinating and ubiquitin ligase activity-dependent manner. Although recent studies revealed that A20 regulates NF-kappa B independently of its enzymatic activity through its seventh zinc finger motif (ZnF7), the involvement of ZnF7 in TNF-alpha-induced apoptosis is not clear. In this study, ZnF7 was found to be important for A20-mediated suppression of TNF-alpha-induced apoptosis. We also found that the ubiquitin ligases cIAP1/2 are required for A20 to suppress TNF-alpha-induced apoptosis. Because A20 binds to cIAP1/2 through ZnF7, these results suggest that A20 may control cIAP1/2 when suppressing TNF-alpha-induced apoptosis. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.