Tankyrase-mediated ADP-ribosylation is a regulator of TNF-induced death
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
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Creation Date: 2022-05-13 08:15:16
Last Modified: 2022-05-13 08:16:02
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