| First Author | Okondo MC | Year | 2018 |
| Journal | Cell Chem Biol | Volume | 25 |
| Issue | 3 | Pages | 262-267.e5 |
| PubMed ID | 29396289 | Mgi Jnum | J:273615 |
| Mgi Id | MGI:6284904 | Doi | 10.1016/j.chembiol.2017.12.013 |
| Citation | Okondo MC, et al. (2018) Inhibition of Dpp8/9 Activates the Nlrp1b Inflammasome. Cell Chem Biol 25(3):262-267.e5 |
| abstractText | Val-boroPro (PT-100, Talabostat) induces powerful anti-tumor immune responses in syngeneic cancer models, but its mechanism of action has not yet been established. Val-boroPro is a non-selective inhibitor of post-proline-cleaving serine proteases, and the inhibition of the highly related cytosolic serine proteases Dpp8 and Dpp9 (Dpp8/9) by Val-boroPro was recently demonstrated to trigger an immunostimulatory form of programmed cell death known as pyroptosis selectively in monocytes and macrophages. Here we show that Dpp8/9 inhibition activates the inflammasome sensor protein Nlrp1b, which in turn activates pro-caspase-1 to mediate pyroptosis. This work reveals a previously unrecognized mechanism for activating an innate immune pattern recognition receptor and suggests that Dpp8/9 serve as an intracellular checkpoint to restrain Nlrp1b and the innate immune system. |
