NLRP1 inflammasome Activation


Event details

Date 23.03.2021
Hour 16:1517:15
Speaker Dr. Daniel Bachovchin is an Assistant Professor in the Chemical Biology Program at the Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center. His lab uses chemical and cell biology approaches to study proteins and pathways involved in innate immunity, in particular inflammasomes. Dr. Bachovchin received his Ph.D. in 2011 from The Scripps Research Institute under the guidance of Dr. Benjamin F. Cravatt.  From 2011-2015, Dr. Bachovchin was a postdoctoral fellow in Dr. Todd Golub’s laboratory at The Broad Institute.       
Location Online
Category Conferences - Seminars

Intracellular pathogens and danger signals trigger the formation of inflammasomes, which activate inflammatory caspases and induce pyroptosis. The anthrax lethal factor metalloprotease and small-molecule inhibitors of the serine proteases DPP8/9 both activate the NLRP1 inflammasome.

We recently discovered lethal factor lethal factor directly cleaves NLRP1, triggering the N-end rule-mediated degradation of the NLRP1B N-terminus and freeing the NLRP1 C-terminus to activate caspase-1.

We found that DPP8/9 inhibitors also induce proteasomal degradation of the NLRP1 N-terminus, but not via the N-end rule pathway. In order to elucidate the mechanism of DPP8/9 inhibitor-induced pyroptosis, we developed and applied a new chemical strategy for protease substrate profiling called CHOPS.

Using CHOPS, we found that DPP8/9 cleave small peptides but not globular proteins. We anticipate that future studies will reveal how DPP8/9 protease activity on these peptides restrains NLRP1 and the immune system.



Practical information

  • General public
  • Free


  • Prof Yimon Aye