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P3: Proteases in inflammasome activity

Proteases and substrates as initiators and executioners of inflammasome activity (PI Olaf Groß)

Proteolysis plays multifaceted roles in inflammasome signalling and biology and related cell death modalities. Within ProtPath, we investigate the roles of proteases and their substrates in the context of the NLRP1 and NLRP3 inflammasomes. We are especially interested in the cathepsin substrates involved in lytic cell death and NLRP3 activation upon lysosomal damage in macrophages.

Overview of inflammasome biology. Underlined are
stimuli used in this project. NLRP3, here activated by the
pore-forming toxin Nigericin, exclusively engages caspase-1
through ASC. In the NLRP1 inflammasome, pro-caspase-1 is
active for GSDMD cleavage and pyroptosis, but ASC is required
for auto- and IL-1β processing.