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| Status |
Public on Sep 19, 2022 |
| Title |
Caspase-8 and FADD prevent spontaneous ZBP1 expression and necroptosis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Caspase-8 and FADD play key roles in the regulation of cell death by necroptosis. The absence of either protein results in early embryonic lethality due to the activation of the kinase RIPK3 and its phosphorylation of the necroptosis executioner, MLKL. We genetically engineered and characterized a mouse model to monitor MLKL phosphorylation in the absence of necroptosis in vivo. Ablation of caspase-8 or FADD resulted in the transcriptional upregulation in several tissues of ZBP1, a cytosolic nucleic acid sensor capable of activating RIPK3, and ZBP1 was required for spontaneous phosphorylation of MLKL. Our findings provide a novel mechanism by which the FADD-Caspase-8 complex prevents necroptosis.
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| Overall design |
Here we performed RNAseq screening to identify gene expression in the absence or presence of Caspase-8 or FADD
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| Contributor(s) |
Rodriguez DA, Tummer B, Chen MJ, Crawford JC, Green DR |
| Citation(s) |
36191211 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 AI044828 |
Survival Function of the Fadd-Caspase-8-Flip Complex |
ST. JUDE CHILDREN'S RESEARCH HOSPITAL |
DOUGLAS R GREEN |
| R35 CA231620 |
Mechanisms of Regulated Cell Death |
ST. JUDE CHILDREN'S RESEARCH HOSPITAL |
DOUGLAS R GREEN |
| R37 AI044828 |
Survival Function of the Fadd-Caspase-8-Flip Complex - MERIT Extension |
ST. JUDE CHILDREN'S RESEARCH HOSPITAL |
DOUGLAS R GREEN |
| P30 CA021765 |
Cancer Center Support Grant (CCSG) |
ST. JUDE CHILDREN'S RESEARCH HOSPITAL |
CHARLES ROBERTS |
| P30 CA006927 |
Comprehensive Cancer Center Program at Fox Chase |
Institute for Cancer Research |
JONATHAN D. CHERNOFF |
| R01 AI135025 |
Mechanism, Function, and Exploitation of Influenza A Virus-Activated Cell Death |
Institute for Cancer Research |
SIDDHARTH BALACHANDRAN |
| R01 AI144400 |
Targeting RIPK3 in Flu-Associated Lung Injury |
Institute for Cancer Research |
SIDDHARTH BALACHANDRAN |
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| |
| Submission date |
Jul 21, 2022 |
| Last update date |
Dec 06, 2022 |
| Contact name |
Douglas R Green |
| E-mail(s) |
douglas.green@stjude.org
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| Organization name |
St Jude Children's Research Hospital
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| Department |
Immunology
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| Lab |
Green lab
|
| Street address |
262 Danny Thomas Pl
|
| City |
Memphis |
| State/province |
United States |
| ZIP/Postal code |
38105 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (12)
|
| GSM6368763 |
MEFs Fadd and Mlkl knock-out with ectopic-reexpression of Fadd rep 1 |
| GSM6368764 |
MEFs Fadd and Mlkl knock-out with ectopic-reexpression of Fadd rep 2 |
| GSM6368765 |
MEFs Fadd and Mlkl knock-out with ectopic-reexpression of Fadd rep 3 |
| GSM6368766 |
MEFs Casp8 and Mlkl knock-out rep 1 |
| GSM6368767 |
MEFs Casp8 and Mlkl knock-out rep 2 |
| GSM6368768 |
MEFs Casp8 and Mlkl knock-out rep 3 |
| GSM6368769 |
MEFs Casp8 and Mlkl knock-out with ectopic-reexpression of Casp8 rep 1 |
| GSM6368770 |
MEFs Casp8 and Mlkl knock-out with ectopic-reexpression of Casp8 rep 2 |
| GSM6368771 |
MEFs Casp8 and Mlkl knock-out with ectopic-reexpression of Casp8 rep 3 |
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| Relations |
| BioProject |
PRJNA860938 |
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