Tankyrase-mediated ADP-ribosylation is a regulator of TNF-induced death

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; John Silke

doi:10.1126/sciadv.abh2332

Tankyrase-mediated ADP-ribosylation is a regulator of TNF-induced death

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^*, John Silke^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	eabh2332
Journal	Science Advances
Volume	8
Issue number	19
DOIs	https://doi.org/10.1126/sciadv.abh2332
Publication status	Published - 1 May 2022

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Liu, L., Sandow, J. J., Leslie Pedrioli, D. M., Samson, A. L., Silke, N., Kratina, T., Ambrose, R. L., Doerflinger, M., Hu, Z., Morrish, E., Chau, D., Kueh, A. J., Fitzibbon, C., Pellegrini, M., Pearson, J. S., Hottiger, M. O., Webb, A. I., Lalaoui, N., & Silke, J. (2022). Tankyrase-mediated ADP-ribosylation is a regulator of TNF-induced death. Science Advances, 8(19), Article eabh2332. https://doi.org/10.1126/sciadv.abh2332

@article{0d5aefc225f849b2a326182c5c520df1,

title = "Tankyrase-mediated ADP-ribosylation is a regulator of TNF-induced death",

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.",

author = "Lin Liu and Sandow, {Jarrod J.} and {Leslie Pedrioli}, {Deena M.} and Samson, {Andre L.} and Natasha Silke and Tobias Kratina and Ambrose, {Rebecca L.} and Marcel Doerflinger and Zhaoqing Hu and Emma Morrish and Diep Chau and Kueh, {Andrew J.} and Cheree Fitzibbon and Marc Pellegrini and Pearson, {Jaclyn S.} and Hottiger, {Michael O.} and Webb, {Andrew I.} and Najoua Lalaoui and John Silke",

note = "This work was funded by NHMRC grants 1145888 and 1163581 and fellowship 1107149 (JS 2016-2020) and was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS (9000433). N.L. is supported by a Victorian Cancer Agency Mid-Career Research Fellowship no. 17030. Research in the laboratory of M.O.H. is funded by the Canton of Zurich and the Swiss National Science Foundation (grant 310030A_176177). The generation of the Casp8N3FLAG, Casp8C3FLAG, and Tnks2−/− mice used in this study was supported by the Australian Phenomics Network (APN) and the Australian Government through the National Collaborative Research Infrastructure Strategy (NCRIS) program.",

year = "2022",

month = may,

day = "1",

doi = "10.1126/sciadv.abh2332",

language = "English",

volume = "8",

journal = "Science Advances",

issn = "2375-2548",

publisher = "American Association for the Advancement of Science",

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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 2022, 'Tankyrase-mediated ADP-ribosylation is a regulator of TNF-induced death', Science Advances, vol. 8, no. 19, eabh2332. https://doi.org/10.1126/sciadv.abh2332

TY - JOUR

T1 - Tankyrase-mediated ADP-ribosylation is a regulator of TNF-induced death

AU - Liu, Lin

AU - Sandow, Jarrod J.

AU - Leslie Pedrioli, Deena M.

AU - Samson, Andre L.

AU - Silke, Natasha

AU - Kratina, Tobias

AU - Ambrose, Rebecca L.

AU - Doerflinger, Marcel

AU - Hu, Zhaoqing

AU - Morrish, Emma

AU - Chau, Diep

AU - Kueh, Andrew J.

AU - Fitzibbon, Cheree

AU - Pellegrini, Marc

AU - Pearson, Jaclyn S.

AU - Hottiger, Michael O.

AU - Webb, Andrew I.

AU - Lalaoui, Najoua

AU - Silke, John

N1 - This work was funded by NHMRC grants 1145888 and 1163581 and fellowship 1107149 (JS 2016-2020) and was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS (9000433). N.L. is supported by a Victorian Cancer Agency Mid-Career Research Fellowship no. 17030. Research in the laboratory of M.O.H. is funded by the Canton of Zurich and the Swiss National Science Foundation (grant 310030A_176177). The generation of the Casp8N3FLAG, Casp8C3FLAG, and Tnks2−/− mice used in this study was supported by the Australian Phenomics Network (APN) and the Australian Government through the National Collaborative Research Infrastructure Strategy (NCRIS) program.

PY - 2022/5/1

Y1 - 2022/5/1

N2 - 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.

AB - 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.

U2 - 10.1126/sciadv.abh2332

DO - 10.1126/sciadv.abh2332

M3 - Article

C2 - 35544574

AN - SCOPUS:85129951973

SN - 2375-2548

VL - 8

JO - Science Advances

JF - Science Advances

IS - 19

M1 - eabh2332

ER -

Tankyrase-mediated ADP-ribosylation is a regulator of TNF-induced death

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