1. Tankyrase-mediated ADP-ribosylation is a regulator of TNF-induced death
- Author
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Lin Liu, Jarrod J. Sandow, Deena M. Leslie Pedrioli, Andre L. Samson, Natasha Silke, Tobias Kratina, Rebecca L. Ambrose, Marcel Doerflinger, Zhaoqing Hu, Emma Morrish, Diep Chau, Andrew J. Kueh, Cheree Fitzibbon, Marc Pellegrini, Jaclyn S. Pearson, Michael O. Hottiger, Andrew I. Webb, Najoua Lalaoui, and John Silke
- Subjects
Multidisciplinary - Abstract
Tumor necrosis factor (TNF) is a key component of the innate immune response. Upon binding to its receptor, TNFR1, it promotes production of other cytokines via a membrane-bound complex 1 or induces cell death via a cytosolic complex 2. To understand how TNF-induced cell death is regulated, we performed mass spectrometry of complex 2 and identified tankyrase-1 as a native component that, upon a death stimulus, mediates complex 2 poly–ADP-ribosylation (PARylation). PARylation promotes recruitment of the E3 ligase RNF146, resulting in proteasomal degradation of complex 2, thereby limiting cell death. Expression of the ADP-ribose–binding/hydrolyzing severe acute respiratory syndrome coronavirus 2 macrodomain sensitizes cells to TNF-induced death via abolishing complex 2 PARylation. This suggests that disruption of ADP-ribosylation during an infection can prime a cell to retaliate with an inflammatory cell death.
- Published
- 2022