Yamaguchi Noritaka, Yamaguchi Naoto
Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
FEBS Lett. 2015 May 22;589(12):1369-75. doi: 10.1016/j.febslet.2015.04.022. Epub 2015 Apr 22.
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.
泛素编辑酶A20以去泛素化和泛素连接酶活性依赖的方式抑制核因子-κB（NF-κB）激活以及肿瘤坏死因子-α（TNF-α）诱导的凋亡。尽管最近的研究表明A20通过其第七个锌指基序（ZnF7）独立于其酶活性调节NF-κB，但ZnF7在TNF-α诱导的凋亡中的作用尚不清楚。在本研究中，发现ZnF7对于A20介导的TNF-α诱导凋亡的抑制作用很重要。我们还发现泛素连接酶cIAP1/2是A20抑制TNF-α诱导凋亡所必需的。由于A20通过ZnF7与cIAP1/2结合，这些结果表明A20在抑制TNF-α诱导凋亡时可能调控cIAP1/2。
