September 2022 — Vol 142 No 9

Molecular mechanisms underlying NLRP1 activation

In this issue of the Journal of Investigative Dermatology, Fenini et al describe the four mechanisms of NLRP1 activation: (a) proteolytic cleavage of N-NLRP1 between DLR1 and DLR2 by 3C proteases of picornaviruses; (b) Talabostat activates NLRP1 during inhibition of DPP9 and release of C-NLRP1 and N-NLRP1; (c) NLRP1 activation by double-stranded RNA derived from alphaviruses and binding of dsRNA to the leucine-rich repeat (LRRs) and phosphorylation of N-NLRP1; (d) UVB or certain bacterial toxins activate the ribotoxic stress response (RSR) and induce through ZAKα and downstream p38 N-NLRP1 phosphorylation. For full details, see the article on page 2313.