Title : Inhibition of Dpp8\/9 Activates the Nlrp1b Inflammasome - Okondo_2018_Cell.Chem.Biol_25_262 |
Author(s) : Okondo MC , Rao SD , Taabazuing CY , Chui AJ , Poplawski SE , Johnson DC , Bachovchin DA |
Ref : Cell Chemical Biology , 25 :262 , 2018 |
Abstract :
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. |
PubMedSearch : Okondo_2018_Cell.Chem.Biol_25_262 |
PubMedID: 29396289 |
Gene_locus related to this paper: human-DPP8 , human-DPP9 |
Inhibitor | Talabostat |
Gene_locus | human-DPP8 human-DPP9 |
Okondo MC, Rao SD, Taabazuing CY, Chui AJ, Poplawski SE, Johnson DC, Bachovchin DA (2018)
Inhibition of Dpp8\/9 Activates the Nlrp1b Inflammasome
Cell Chemical Biology
25 :262
Okondo MC, Rao SD, Taabazuing CY, Chui AJ, Poplawski SE, Johnson DC, Bachovchin DA (2018)
Cell Chemical Biology
25 :262