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. 2017 May 11;8:15203. doi: 10.1038/ncomms15203

Figure 7. NALP7 inflammasome activity requires STAMBP DUB activity that is antagonized by BC-1471.

Figure 7

In the absence of inflammatory stimuli, NALP7 is constitutively ubiquitinated (1) and bound by STAM as cargo for endosomal trafficking (2). Ub-NALP7 is shuttled to the lysosome for degradation (3). STAMBP deubiquitinates Ub-NALP7 facilitating NALP7 recue from degradation (4). With LPS or Pam3CSK4 exposure, NALP7 protein abundance increases (5) by decreasing endolysosomal trafficking in a process dependent on the DUB activity of STAMBP. The NALP7 inflammasome assembles in response to LPS or Pam3CSK4 (6) with subsequent IL-1β cleavage to its active form and inflammatory signalling. BC-1471 antagonizes STAMBP DUB activity (7), inhibiting NALP7 rescue, downstream of inflammasome assembly and IL-1β maturation.