Tankyrase-mediated ADP-ribosylation is a regulator of TNF-induced death
- Liu, L; Sandow, JJ; Leslie Pedrioli, DM; Samson, AL; Silke, N; Kratina, T; Ambrose, RL; Doerflinger, M; Hu, Z; Morrish, E; Chau, D; Kueh, AJ; Fitzibbon, C; Pellegrini, M; Pearson, JS; Hottiger, MO; Webb, AI; Lalaoui, N; Silke, J;
- Publication Year 2022-05-13,Volume 8,Issue #19,Page eabh2332
- Journal Title
- Science Advances
- 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.
- WEHI Research Division(s)
- Inflammation; Advanced Technology And Biology; Blood Cells And Blood Cancer; Infectious Diseases And Immune Defence
- PubMed ID
- Publisher's Version
- Refer to copyright notice on published article.
Creation Date: 2022-05-13 08:15:16Last Modified: 2022-05-13 08:16:02