Matches in SemOpenAlex for { <https://semopenalex.org/work/W2922373211> ?p ?o ?g. }
- W2922373211 abstract "Abstract NLRC4 is an innate immune receptor, which upon detection of certain pathogens or internal distress signal, initiates caspase-1 mediated inflammatory response. A gain-of-function mutation, H443P in NLRC4, causes familial cold autoinflammatory syndrome (FCAS) characterized by cold-induced hyperactivation of caspase-1 and inflammation. Here, we show that heat shock cognate protein 70 (HSC70) complexes with NLRC4 and negatively regulates caspase-1 activation by NLRC4-H443P. Compared to NLRC4, the structurally altered NLRC4-H443P shows enhanced interaction with HSC70. Knockdown of HSC70 or inhibition of its ATPase activity enhances caspase-1 activation by NLRC4-H443P. Exposure to subnormal temperature resulted in reduced interaction of NLRC4-H443P with HSC70, and an increase in its ability to form ASC-specks and activate caspase-1. By demonstrating that HSC70 differentially interacts with NLRC4-H443P mutant in a temperature-dependent manner to regulate caspase-1 activation, we provide a mechanism for cold-induced inflammation seen in FCAS patients with NLRC4-H443P mutation." @default.
- W2922373211 created "2019-03-22" @default.
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- W2922373211 date "2019-03-15" @default.
- W2922373211 modified "2023-09-25" @default.
- W2922373211 title "HSC70 regulates cold-induced caspase-1 hyperactivation by an autoinflammation-causing mutant of cytoplasmic immune receptor NLRC4" @default.
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- W2922373211 doi "https://doi.org/10.1101/578138" @default.
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