TAK1 integrates the NLRP1 inflammasome into the innate immune response to double-stranded RNA
Corley, M. R.; Hyodo, A.; Toyoda, H. C.; Yonemitsu, M. A.; Chantharath, A.; Hyde, J. L.; Mitchell, P. S.
Show abstract
Innate immune recognition of double-stranded RNA (dsRNA) by germline-encoded receptors initiates antiviral defenses, including type I interferon (IFN) production. The inflammasome-forming sensor NLRP1 binds and is activated by dsRNA in a mitogen-activated protein kinase (MAPK) p38-dependent manner. How dsRNA initiates these events to induce NLRP1 inflammasome activation is unclear. Here we demonstrate that both exogenous and cellular dsRNA triggers NLRP1 inflammasome activation downstream of RIG-I/MDA5-MAVS and/or TLR3-TRIF signaling but is independent of type I IFN. In immortalized and primary human keratinocytes, we find that NLRP1 inflammasome activation by dsRNA, including during viral infection, requires the MAPK kinase kinase TAK1. Mechanistically, TAK1-dependent phosphorylation of the NLRP1 N-terminal disordered region is necessary and sufficient for inflammasome activation. Collectively, we reveal TAK1 as a novel activator of the NLRP1 inflammasome, functioning as a critical signaling hub linking NLRP1 to inflammatory responses in the context of viral infection and autoimmunity.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- A basally active cGAS-STING pathway limits SARS-CoV-2 replication in a subset of ACE2 positive airway cell models 97%
- Antagonistic nanobodies reveal mechanism of GSDMD pore formation and unexpected therapeutic potential 97%
- Proximal protein landscapes of the type I interferon signaling cascade reveal negative regulation by the E3 ubiquitin ligase PJA2 96%
Similar papers in this journal
- Noncanonical inflammasome assembly requires caspase-11 catalytic activity and intra-molecular autoprocessing 96%
- A human-specific motif facilitates CARD8 inflammasome activation after HIV-1 infection 96%
- ORMDL3 restrains type-I interferon signaling and anti-tumor immunity by promoting RIG-I degradation 96%
Similar papers in this journal
- NLRP3 Cys126 palmitoylation by ZDHHC7 Promotes Inflammasome Activation 95%
- Alternate isoforms of IRF7 Differentially Regulate Interferon Expression to Tune Response to Viral Infection 95%
- Mitochondrial cyclophilin D promotes disease tolerance by licensing NK cell development and IL-22 production against influenza virus 95%
Similar papers in this journal
- MDA5 ISGylation is crucial for immune signaling to control viral replication and pathogenesis 96%
- Caspase-4/11 exacerbates disease severity in SARS-CoV-2 infection by promoting inflammation and thrombosis 95%
- Immune dysregulation in SHARPIN-deficient mice is dependent on CYLD-mediated cell death 94%
Similar papers in this journal
- Plasmacytoid dendritic cells are dispensable or detrimental in murine systemic or respiratory viral infections 95%
- A negative feedback loop mediated by the NR4A family of nuclear hormone receptors restrains expansion of B cells that receive signal one in the absence of signal two 94%
- Loss of the intracellular enzyme QPCTL limits chemokine function and reshapes myeloid infiltration to augment tumor immunity 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.