A5030761924- Inflammasome and immune disorders
- Heme Oxygenase-1 and Carbon Monoxide
- Endoplasmic Reticulum Stress and Disease
- Peptidase Inhibition and Analysis
- Tryptophan and brain disorders
- Ubiquitin and proteasome pathways
Memorial Sloan Kettering Cancer Center
2022-2023
The danger signals that activate the related nucleotide-binding domain leucine-rich repeat pyrin domain-containing 1 (NLRP1) and caspase activation recruitment 8 (CARD8) inflammasomes have not been fully established. We recently reported oxidized form of TRX1 binds to NLRP1 represses inflammasome activation. These findings suggested intracellular reductive stress, which would reduce thereby abrogate NLRP1-TRX1 interaction, is an inflammasome-activating signal. However, no agents induce...
NLRP1 and CARD8 are related pattern-recognition receptors (PRRs) that detect intracellular danger signals form inflammasomes. Both undergo autoproteolysis, generating N-terminal (NT) C-terminal (CT) fragments. The proteasome-mediated degradation of the NT releases CT from autoinhibition, but stimuli trigger have not been fully elucidated. Here, we show several distinct agents interfere with protein folding, including aminopeptidase inhibitors, chaperone inducers unfolded response, accelerate...
The danger signals that activate the NLRP1 and CARD8 inflammasomes have not been fully established. We recently discovered cytosolic peptide accumulation activates these inflammasomes. In addition, we found oxidized form of TRX1 binds to represses NLRP1, suggesting also detects a lack reactive oxygen species, or reductive stress. However, no agents induce stress were known test this premise. Here, identify characterize several radical-trapping antioxidants, including JSH-23, show compounds...
NLRP1 and CARD8 are related sensors that form inflammasomes, but the danger signals they detect not fully established. These proteins undergo autoproteolysis, generating repressive N-terminal (NT) inflammatory C-terminal (CT) fragments. The proteasome-mediated degradation of NT releases CT from autoinhibition, is then sequestered in a complex with full-length sensor DPP9. Here, we show cytosolic peptide accumulation activates these inflammasomes. We found diverse array peptides accelerates...