Anthrax Lethal Factor Cleaves the N-Terminus of MAPKKs and Induces Tyrosine/Threonine Phosphorylation of MAPKs in Cultured Macrophages

1998 ◽  
Vol 248 (3) ◽  
pp. 706-711 ◽  
Author(s):  
Gaetano Vitale ◽  
Rossella Pellizzari ◽  
Chiara Recchi ◽  
Giorgio Napolitani ◽  
Michèle Mock ◽  
...  
Keyword(s):  
Lethal Factor ◽  
Anthrax Lethal Factor ◽  
N Terminus

scholarly journals N-terminal degradation activates the Nlrp1b inflammasome

2018 ◽  
Author(s):  
Ashley J. Chui ◽  
Marian C. Okondo ◽  
Sahana D. Rao ◽  
Kuo Gai ◽  
Andrew R. Griswold ◽  
...  
Keyword(s):  
Cell Death ◽  
Lethal Factor ◽  
Proteasomal Degradation ◽  
Degradation Pathway ◽  
Common Mechanism ◽  
Caspase 1 ◽  
C Terminus ◽  
Anthrax Lethal Factor ◽  
N Terminus ◽  
Inflammatory Caspases

AbstractIntracellular pathogens and danger signals trigger the formation of inflammasomes, which activate inflammatory caspases and induce pyroptotic cell death. The anthrax lethal factor metalloprotease and small molecule DPP8/9 inhibitors both activate the Nlrp1b inflammasome, but the molecular mechanism of Nlrp1b activation is not known. Here, we used genome-wide CRISPR/Cas9 knockout screens to identify genes required for Nlrp1b-mediated pyroptosis, and discovered that lethal factor induces cell deathviathe N-end rule proteasomal degradation pathway. Lethal factor directly cleaves Nlrp1b, which induces the N-end rule-mediated degradation of the Nlrp1b N-terminus and thereby frees the Nlrp1b C-terminus to activate caspase-1. DPP8/9 inhibitors also induce proteasomal degradation of the Nlrp1b N-terminus, but, in contrast, not through the N-end rule pathway. Overall, these data reveal that N-terminal degradation is the common mechanism for activation of this innate immune sensor protein.One Sentence SummaryProteasome-mediated degradation of the Nlrp1b N-terminus releases the Nlrp1b C-terminus to activate caspase-1 and induce pyroptotic cell death.

scholarly journals N-terminal degradation activates the NLRP1B inflammasome

Science ◽  
2019 ◽  
Vol 364 (6435) ◽  
pp. 82-85 ◽  
Author(s):  
Ashley J. Chui ◽  
Marian C. Okondo ◽  
Sahana D. Rao ◽  
Kuo Gai ◽  
Andrew R. Griswold ◽  
...  
Keyword(s):  
Lethal Factor ◽  
Proteasomal Degradation ◽  
Degradation Pathway ◽  
Activation Mechanism ◽  
C Terminus ◽  
Anthrax Lethal Factor ◽  
Genome Wide ◽  
N Terminus ◽  
The Common ◽  
Inflammatory Caspases

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 DPP8/9 inhibitors both activate the NLRP1B inflammasome, but the molecular mechanism of NLRP1B activation is unknown. In this study, we used genome-wide CRISPR-Cas9 knockout screens to identify genes required for NLRP1B-mediated pyroptosis. We discovered that lethal factor induces cell death via the N-end rule proteasomal degradation pathway. Lethal factor directly cleaves NLRP1B, inducing the N-end rule–mediated degradation of the NLRP1B N terminus and freeing the NLRP1B C terminus to activate caspase-1. DPP8/9 inhibitors also induce proteasomal degradation of the NLRP1B N terminus but not via the N-end rule pathway. Thus, N-terminal degradation is the common activation mechanism of this innate immune sensor.

Anthrax lethal factor cleaves the N-terminus of MAPKKS and induces tyrosine/threonine phosphorylation of MAPKS in cultured macrophages

1999 ◽  
Vol 87 (2) ◽  
pp. 288-288 ◽  
Author(s):  
G. Vitale ◽  
R. Pellizzari ◽  
C. Recchi ◽  
G. Napolitani ◽  
M. Mock ◽  
...  
Keyword(s):  
Lethal Factor ◽  
Anthrax Lethal Factor ◽  
N Terminus

Label-Free Electrochemical Detection of DNA Hybridization Related to Anthrax Lethal Factor by using Carbon Nanotube Modified Sensors

2019 ◽  
Vol 15 (4) ◽  
pp. 502-510 ◽  
Author(s):  
Hakan Karadeniz ◽  
Arzum Erdem
Keyword(s):  
Detection Limit ◽  
Dna Hybridization ◽  
Lethal Factor ◽  
Modified Electrodes ◽  
Label Free ◽  
Carbon Paste ◽  
Chip Technology ◽  
Anthrax Lethal Factor ◽  
Hybridization Time ◽  
Electrochemical Monitoring

Background: Anthrax Lethal Factor (ANT) is the dominant virulence factor produced by B. anthracis and is the major cause of death of infected animals. In this paper, pencil graphite electrodes GE were modified with single-walled and multi-walled carbon nanotubes (CNTs) for the detection of hybridization related to the ANT DNA for the first time in the literature. Methods: The electrochemical monitoring of label-free DNA hybridization related to ANT DNA was explored using both SCNT and MCNT modified PGEs with differential pulse voltammetry (DPV). The performance characteristics of ANT-DNA hybridization on disposable GEs were explored by measuring the guanine signal in terms of optimum analytical conditions; the concentration of SCNT and MCNT, the concentrations of probe and target, and also the hybridization time. Under the optimum conditions, the selectivity of probe modified electrodes was tested and the detection limit was calculated. Results: The selectivity of ANT probes immobilized onto MCNT-GEs was tested in the presence of hybridization of probe with NC no response was observed and with MM, smaller responses were observed in comparison to full-match DNA hybridization case. Even though there are unwanted substituents in the mixture samples containing both the target and NC in the ratio 1:1 and both the target and MM in the ratio 1:1, it has been found that ANT probe immobilized CNT modified graphite sensor can also select its target by resulting with 20.9% decreased response in comparison to the one measured in the case of full-match DNA hybridization case Therefore, it was concluded that the detection of direct DNA hybridization was performed by using MCNT-GEs with an acceptable selectivity. Conclusion: Disposable SCNT/MCNT modified GEs bring some important advantages to our assay including easy use, cost-effectiveness and giving a response in a shorter time compared to unmodified PGE, carbon paste electrode and glassy carbon electrode developed for electrochemical monitoring of DNA hybridization. Consequently, the detection of DNA hybridization related to the ANT DNA by MCNT modified sensors was performed by using lower CNT, probe and target concentrations, in a shorter hybridization time and resulting in a lower detection limit according to the SCNT modified sensors. In conclusion, MCNT modified sensors can yield the possibilities leading to the development of nucleic acid sensors platforms for the improvement of fast and cost-effective detection systems with respect to DNA chip technology.

Inhibitors of anthrax lethal factor

2007 ◽  
Vol 17 (16) ◽  
pp. 4575-4578 ◽  
Author(s):  
Brandon D. Gaddis ◽  
Larisa V. Avramova ◽  
Jean Chmielewski
Keyword(s):  
Lethal Factor ◽  
Anthrax Lethal Factor

Insilico studies on anthrax lethal factor inhibitors: Pharmacophore modeling and virtual screening approaches towards designing of novel inhibitors for a killer

2010 ◽  
Vol 29 (2) ◽  
pp. 256-265 ◽  
Author(s):  
Jyoti Roy ◽  
Uday Chandra Kumar ◽  
Pavan Kumar Machiraju ◽  
Ravi Kumar Muttineni ◽  
Suneel Kumar B.V.S ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Lethal Factor ◽  
Pharmacophore Modeling ◽  
Anthrax Lethal Factor ◽  
Screening Approaches

scholarly journals Influence of chemical denaturants on the activity, fold and zinc status of anthrax lethal factor

2015 ◽  
Vol 1 ◽  
pp. 68-77
Author(s):  
Suet Y. Lo ◽  
Crystal E. Säbel ◽  
Jonathan P.J. Mapletoft ◽  
Stefan Siemann
Keyword(s):  
Lethal Factor ◽  
Zinc Status ◽  
Anthrax Lethal Factor
Sign in / Sign up

Export Citation Format

Share Document