Mechanisms of NLRP1-Mediated Autoinflammatory Disease in Humans and Mice
Chien-Hsiung Yu, Jonas Moecking, Matthias Geyer, Seth L Masters
JOURNAL OF MOLECULAR BIOLOGY | ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD | Published : 2018
NLRP1 was the first NOD-like receptor described to form an inflammasome, recruiting ASC to activate caspase-1, which processes interleukin-1β and interleukin-18 to their active form. A wealth of new genetic information has now redefined our understanding of this innate immune sensor. Specifically, rare loss-of-function variants in the N-terminal pyrin domain indicate that this part of NLRP1 is autoinhibitory and normally acts to prevent a familial autoinflammatory skin disease associated with cancer. In the absence of a ligand to trigger human NLRP1, these mutations have now confirmed the requirement of NLRP1 autolytic cleavage within the FIIND domain, which had previously been implicated in..View full abstract
Awarded by Bonn & Melbourne Graduate School BoMeRanG
Awarded by Australian National Health and Medical Research Council
C.-H.Y. is a recipient of WEHI Centenary Fellowship and Ormond College's Thwaites Gutch Fellowship in Physiology. J.M. is funded by the Bonn & Melbourne Graduate School Bo&MeRanG (GRK 2168). M.G. is a member of the DFG excellence cluster Immuno-Sensation. S.L.M. received funding from an Australian National Health and Medical Research Council project grant (1099262), the Viertel Foundation, and Glaxosmithkline. The authors declare no competing interests.