A5089448977- Inflammasome and immune disorders
- Heme Oxygenase-1 and Carbon Monoxide
- interferon and immune responses
- Neonatal Health and Biochemistry
- Protein Kinase Regulation and GTPase Signaling
- Bacterial Infections and Vaccines
- Immune Response and Inflammation
- Wnt/β-catenin signaling in development and cancer
- Lipid Membrane Structure and Behavior
- Autoimmune and Inflammatory Disorders Research
- Bartonella species infections research
- Streptococcal Infections and Treatments
- Ubiquitin and proteasome pathways
- Gout, Hyperuricemia, Uric Acid
- Rabies epidemiology and control
- Vector-borne infectious diseases
- Viral Infections and Vectors
- Erythrocyte Function and Pathophysiology
- Fibroblast Growth Factor Research
- Cell death mechanisms and regulation
- IL-33, ST2, and ILC Pathways
University of Basel
1995-2018
Abstract A hallmark of inflammasome activation is the ASC speck, a micrometre-sized structure formed by adaptor protein (apoptosis-associated speck-like containing CARD), which consists pyrin domain (PYD) and caspase recruitment (CARD). Here we show that assembly speck involves oligomerization PYD into filaments cross-linking these CARD . mutants with non-functional only assemble but not specks, moreover disrupt endogenous specks in primary macrophages. Systematic site-directed mutagenesis...
Abstract The pro‐inflammatory cytokine IL‐1β is well known for its role in host defense and the initiation of potent inflammatory responses. It processed from inactive pro‐form by caspase‐1 into mature bioactive form, which then released cell via an unconventional secretion mechanism. Recently, gasdermin‐D has been identified as a new target caspase‐1. After proteolytical cleavage gasdermin‐D, N‐terminal fragment induces pyroptosis, lytic death, forming large permeability pores plasma...
Inflammasomes activate the protease caspase-1, which cleaves interleukin-1β and interleukin-18 to generate mature cytokines controls their secretion a form of inflammatory cell death called pyroptosis. By generating mice expressing enzymatically inactive caspase-1C284A, we provide genetic evidence that caspase-1 activity is required for canonical IL-1 secretion, pyroptosis, inflammasome-mediated immunity. In caspase-1-deficient cells, caspase-8 can be activated at inflammasome. Using either...
Significance Invading pathogens and other danger-associated signals are recognized by the innate immune system. Subsequently, eukaryotic protein ASC [apoptosis-associated speck-like containing a caspase-recruitment domain (CARD)] assembles to long filaments, which might serve amplify signal activate an inflammatory response. We have determined structure of mouse filament at atomic resolution. The pyrin forms helical core, CARD, thus far elusive experimental observation, is flexibly unfolded...
We have characterized the Drosophila homologue of proto-oncogenic RAC protein kinase (DRAC-PK). The DRAC-PK gene gives rise to two transcripts with same coding potential, generated by use different polyadenylation signals. Each transcript encodes polypeptides because presence a weaker initiator ACG codon, upstream from major AUG, such that larger contains an N-terminal extension. Like human isoforms, DRAC-PKs possess novel signaling region, pleckstrin homology domain. proteins similar...
The co-ordinated expression of virulence factors is a critical process for any bacterial pathogen to colonize its host. Here we investigated the mechanisms niche adaptation zoonotic Bartonella henselae by combining genetic approaches and shotgun proteomics. We demonstrated that VirB/D4 type IV secretion system (T4SS) secreted effector proteins require alternative sigma factor RpoH1, which levels are controlled stringent response (SR) components DksA SpoT. RpoH1-dependent activation requires...
The protein ASC is a central component of most inflammasome complexes, forming functional oligomeric filaments that activate large amounts pro-caspase-1 for further IL-1β processing and the induction Gasdermin D-dependent cell death. role inflammasomes in innate immune response pose them as new molecular targets therapy diverse acute, chronic inherited autoinflammatory pathologies. In recent years, an increasing number molecules were proposed to modulate signalling by interacting with...