Human SV80 Cells: Control vs. Caspase-8 knock down
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Akhil Rajput
PROVIDER: E-GEOD-23363 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Excessive responses to pattern-recognition receptors are prevented by regulatory mechanisms that affect the amounts, conformation, and associative properties of their signaling proteins. We report that signaling by the ribonucleic acid sensor RIG-I is restricted, in addition, by caspase-mediated cleavage that results in conversion of a signaling enhancer to a signaling inhibitor. RIP1 and caspase-8, two proteins known to mediate effects of receptors of the TNF/NGF family, are recruited to the RIG-I complex following viral infection, and serve in a coordinated manner antagonistic regulatory roles: conjugation of a ubiquitin chain to Lys-377 in RIP1 facilitates assembly of the RIG-I complex, but it also renders RIP1 susceptible to caspase-8-mediated cleavage, yielding an inhibitory RIP1 fragment. The dependence of RIP1 cleavage on the same molecular change as the one that facilitates RIG-I signaling allows for RIG-I signaling to be restricted in its duration without compromising its initial activation.
2011-02-07 | GSE23363 | GEO
Project description:Integration of Innate Immune Signaling by 2 Caspase-8-Mediated Cleavage of N4BP1
| MSV000086111 | MassIVE
Project description:The noncanonical inflammasome induced by intracellular lipopolysaccharide (LPS) leads to caspase-11-dependent pyroptosis, which is critical for induction of endotoxic shock in mice. However, the signaling pathway downstream of caspase-11 is unknown. We found that cytosolic LPS stimulation induced caspase-11-dependent cleavage of the pannexin-1 channel followed up by ATP release, which in turn activated the purinergic P2X7 receptor to mediate cytotoxicity. In the absence of P2X7 or pannexin-1, pyroptosis induced by cytosolic LPS was abrogated. Cleavage of pannexin-1 required the catalytic activity of caspase-11 and was essential for ATP release and P2X7-mediated pyroptosis. Priming the caspase-11 pathway in vivo with LPS or Toll-like receptor-3 (TLR3) agonist resulted in high mortality in wild-type mice after secondary LPS challenge, but not in Casp11(-/-), Panx1(-/-), or P2x7(-/-) mice. These results reveal a critical role for pannexin-1 and P2X7 downstream of caspase-11 for pyroptosis and susceptibility to sepsis induced by the noncanonical inflammasome.
Research is published, core data not used but project description is relevant:
http://www.sciencedirect.com/science/article/pii/S1074761315004094
2015-06-05 | ST000174 | MetabolomicsWorkbench
Project description:Mycobacterium tuberculosis is exposed to a variety of stresses during a chronic infection, as the immune system simultaneously produces bactericidal compounds and starves the pathogen for essential nutrients. The intramembrane protease, Rip1, plays an important role in the adaptation to these stresses, at least partially by the cleavage of membrane bound transcriptional regulators. Although Rip1 is known to be critical for surviving copper intoxication and nitric oxide exposure, these stresses do not fully account the regulatory protein’s essentiality during infection. In this work, we demonstrate that Rip1 is also necessary for growth in low iron and zinc conditions, similar to those imposed by the immune system. Using a newly generated library of sigma factor mutants, we show that the known regulatory target of Rip1, SigL, shares this defect. Transcriptional profiling under iron limiting conditions supported the coordinated activity of Rip1 and SigL and demonstrated that the loss of these proteins produces an exaggerated iron starvation response. These observations demonstrate that Rip1 coordinates several aspects of metal homeostasis and suggest that a Rip1- and SigL-dependent pathway is involved in the adaptation to the iron deficient environments encountered during infection.
2023-05-23 | GSE229446 | GEO
Project description:The goal of this study was to determine if knockdown of nicastrin induced a proinflammatory phenotype in HEK001 and HEK293 cells. Nicastrin (NCSTN) is a member of the gamma-secretase complex, and has been identified as the most frequently mutated gene in familial hidradenitis suppurativa. While much research has been done into the effects of PSEN1 and PSEN2 loss, less is known about isolated NCSTN haploinsufficiency. Two cell lines were knocked down with either NCSTN siRNA or an siRNA to luciferase in triplicate. RNA was extracted from drug selected knockdowns and profiled on the Illumina Human HT-12 v4 beadarray. Gene ontology analysis of differentially expressed genes revealed a proinflammatory and decreased proliferation signature in keratinocytes. HEK293 cells demonstrated expression signatures for decreased cholesterol synthesis and interferon-alpha signaling, as well as increased p53 signaling and caspase mediated cytoskeletal cleavage. 12 total samples. Two cell lines (HEK001 & HEK293) each with two treatments (NCSTN siRNA knockdown or pLKO luciferase knockdown) in three parallel 3 replicates each. For each line gives the changes specific to knockdown of gamma-secretase component nicastrin (NCSTN).
2014-11-26 | E-GEOD-57949 | biostudies-arrayexpress
Project description:A comparison of the embryonic transcriptome of wild type embryos (sggisoD-DS-SFS ) with embryos harbouring mutated DEVD caspase recognition sites ( sggisoD-cI-DS-SFS ) in a major shaggy isoforms class to examine the role of caspase cleavage in sgg function. The unique N-terminal exon undegoing caspase cleavage is tagged with DsRED at its N-terminus and StrepII-Flag-StrepII upstream of caspase cleavage sites for the wild type and caspase insensitive variant versions.
2020-09-09 | GSE157625 | GEO
Project description:Receptor-interacting protein kinase 1 (RIP1)-mediated necroptosis plays a vital role in various diseases, but the involvement of RIP1 and its functional mechanism in osteoarthritis pathogenesis remains largely unknown. To identify molecular targets of RIP1 in chondrocytes, RNA sequencing was performed in chondrocytes treated with adenovirus expressing RIP1 or vector control. We found that 9857 genes were differentially expressed in chondrocytes after RIP1 overexpression. GO analysis indicated that DNA replication, chromosome segregation and regulation of cell cycle process were upregulated, while terms including cartilage development, skeletal system development, extracellular matrix organization, skeletal system morphogenesis, chondrocyte differentiation, collagen fibril organization and limb development were downregulated. Pathway analysis revealed that IL-17 signaling pathway, cell cycle, DNA replication, proteasome, TNF signaling pathway, cellular senescence and p53 signaling pathway were significantly upregulated by RIP1, meanwhile, ECM-receptor interaction, other glycan degradation and glycosaminoglycan degradation were downregulated. These results underscore the importance of RIP1 in OA by perturbing a series of essential events during disease progression such like cell cycle regulation, chondrocyte differentiation, inflammation and ECM remodeling.
2021-01-22 | GSE165219 | GEO
Project description:Kallenberger2014 - CD95L induced apoptosis initiated by caspase-8, CD95 HeLa cells (cis/trans variant)
The paper describes a new approach that combines single cell and population data in the same model. The model consists of a large number of single cell models, which are fitted to single cell data. Simultaneously, ensemble averages are fitted to population data. It is assumed that the kinetics in each cell can be described with the same kinetic parameters. Therefore, cell-to-cell variability is explained by variable initial protein concentrations.
There are four variants of the model (with [CD95L]=500ng/ml = 16.6nM), i) cistrans (in CD95-HeLa cells) [ MODEL1403050000
], ii) cistrans (in wild-type HeLa cells) [ MODEL1403050001
], iii) cistrans-cistrans (in CD95-HeLa cells) [ MODEL1403050002
], and iv) cistrans-cistrans (in wild-type HeLa cells) [ MODEL1403050003
].
These model contain the equations for one "average cell" with median initial concentrations for CD95, FADD, p55, BID, PrNES_mCherry and PrER_mGFP. By integrating the model, it should be possible to obtain trajectories for PrER_mGFP, PrNES_mCherry, p43 and p18 similar as in Figure 4A (CD95-HeLa cells) and Figure 4B (wild-type HeLa cells).
This model is described in the article:
Intra- and Interdimeric Caspase-8 Self-Cleavage Controls Strength and Timing of CD95-Induced Apoptosis
Stefan M. Kallenberger, Joël Beaudouin, Juliane Claus, Carmen Fischer, Peter K. Sorger, Stefan Legewie, and Roland Eils
11 March 2014: Vol. 7, Issue 316, p. ra23
Abstract:
Apoptosis in response to the ligand CD95L (also known as Fas ligand) is initiated by caspase-8, which is activated by dimerization and self-cleavage at death-inducing signaling complexes (DISCs). Previous work indicated that the degree of substrate cleavage by caspase-8 determines whether a cell dies or survives in response to a death stimulus. To determine how a death ligand stimulus is effectively translated into caspase-8 activity, we assessed this activity over time in single cells with compartmentalized probes that are cleaved by caspase-8 and used multiscale modeling to simultaneously describe single-cell and population data with an ensemble of single-cell models. We derived and experimentally validated a minimal model in which cleavage of caspase-8 in the enzymatic domain occurs in an interdimeric manner through interaction between DISCs, whereas prodomain cleavage sites are cleaved in an intradimeric manner within DISCs. Modeling indicated that sustained membrane-bound caspase-8 activity is followed by transient cytosolic activity, which can be interpreted as a molecular timer mechanism reflected by a limited lifetime of active caspase-8. The activation of caspase-8 by combined intra- and interdimeric cleavage ensures weak signaling at low concentrations of CD95L and strongly accelerated activation at higher ligand concentrations, thereby contributing to precise control of apoptosis.
This model is hosted on BioModels Database
and identified
by: BIOMD0000000523
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
2024-09-02 | BIOMD0000000523 | BioModels
Project description:Kallenberger2014 - CD95L induced apoptosis initiated by caspase-8, wild-type HeLa cells (cis/trans variant)
The paper describes a new approach that combines single cell and population data in the same model. The model consists of a large number of single cell models, which are fitted to single cell data. Simultaneously, ensemble averages are fitted to population data. It is assumed that the kinetics in each cell can be described with the same kinetic parameters. Therefore, cell-to-cell variability is explained by variable initial protein concentrations.
There are four variants of the model (with [CD95L]=500ng/ml = 16.6nM), i) cistrans (in CD95-HeLa cells) [ MODEL1403050000
], ii) cistrans (in wild-type HeLa cells) [ MODEL1403050001
], iii) cistrans-cistrans (in CD95-HeLa cells) [ MODEL1403050002
], and iv) cistrans-cistrans (in wild-type HeLa cells) [ MODEL1403050003
].
These model contain the equations for one "average cell" with median initial concentrations for CD95, FADD, p55, BID, PrNES_mCherry and PrER_mGFP. By integrating the model, it should be possible to obtain trajectories for PrER_mGFP, PrNES_mCherry, p43 and p18 similar as in Figure 4A (CD95-HeLa cells) and Figure 4B (wild-type HeLa cells).
This model is described in the article:
Intra- and Interdimeric Caspase-8 Self-Cleavage Controls Strength and Timing of CD95-Induced Apoptosis
Stefan M. Kallenberger, Joël Beaudouin, Juliane Claus, Carmen Fischer, Peter K. Sorger, Stefan Legewie, and Roland Eils
11 March 2014: Vol. 7, Issue 316, p. ra23
Abstract:
Apoptosis in response to the ligand CD95L (also known as Fas ligand) is initiated by caspase-8, which is activated by dimerization and self-cleavage at death-inducing signaling complexes (DISCs). Previous work indicated that the degree of substrate cleavage by caspase-8 determines whether a cell dies or survives in response to a death stimulus. To determine how a death ligand stimulus is effectively translated into caspase-8 activity, we assessed this activity over time in single cells with compartmentalized probes that are cleaved by caspase-8 and used multiscale modeling to simultaneously describe single-cell and population data with an ensemble of single-cell models. We derived and experimentally validated a minimal model in which cleavage of caspase-8 in the enzymatic domain occurs in an interdimeric manner through interaction between DISCs, whereas prodomain cleavage sites are cleaved in an intradimeric manner within DISCs. Modeling indicated that sustained membrane-bound caspase-8 activity is followed by transient cytosolic activity, which can be interpreted as a molecular timer mechanism reflected by a limited lifetime of active caspase-8. The activation of caspase-8 by combined intra- and interdimeric cleavage ensures weak signaling at low concentrations of CD95L and strongly accelerated activation at higher ligand concentrations, thereby contributing to precise control of apoptosis.
This model is hosted on BioModels Database
and identified
by: BIOMD0000000524
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
2024-09-02 | BIOMD0000000524 | BioModels
Project description:Kallenberger2014 - CD95L induced apoptosis initiated by caspase-8, CD95 HeLa cells (cis/trans-cis/trans variant)
The paper describes a new approach that combines single cell and population data in the same model. The model consists of a large number of single cell models, which are fitted to single cell data. Simultaneously, ensemble averages are fitted to population data. It is assumed that the kinetics in each cell can be described with the same kinetic parameters. Therefore, cell-to-cell variability is explained by variable initial protein concentrations.
There are four variants of the model (with [CD95L]=500ng/ml = 16.6nM), i) cistrans (in CD95-HeLa cells) [ MODEL1403050000
], ii) cistrans (in wild-type HeLa cells) [ MODEL1403050001
], iii) cistrans-cistrans (in CD95-HeLa cells) [ MODEL1403050002
], and iv) cistrans-cistrans (in wild-type HeLa cells) [ MODEL1403050003
].
These model contain the equations for one "average cell" with median initial concentrations for CD95, FADD, p55, BID, PrNES_mCherry and PrER_mGFP. By integrating the model, it should be possible to obtain trajectories for PrER_mGFP, PrNES_mCherry, p43 and p18 similar as in Figure 4A (CD95-HeLa cells) and Figure 4B (wild-type HeLa cells).
This model is described in the article:
Intra- and Interdimeric Caspase-8 Self-Cleavage Controls Strength and Timing of CD95-Induced Apoptosis
Stefan M. Kallenberger, Joël Beaudouin, Juliane Claus, Carmen Fischer, Peter K. Sorger, Stefan Legewie, and Roland Eils
11 March 2014: Vol. 7, Issue 316, p. ra23
Abstract:
Apoptosis in response to the ligand CD95L (also known as Fas ligand) is initiated by caspase-8, which is activated by dimerization and self-cleavage at death-inducing signaling complexes (DISCs). Previous work indicated that the degree of substrate cleavage by caspase-8 determines whether a cell dies or survives in response to a death stimulus. To determine how a death ligand stimulus is effectively translated into caspase-8 activity, we assessed this activity over time in single cells with compartmentalized probes that are cleaved by caspase-8 and used multiscale modeling to simultaneously describe single-cell and population data with an ensemble of single-cell models. We derived and experimentally validated a minimal model in which cleavage of caspase-8 in the enzymatic domain occurs in an interdimeric manner through interaction between DISCs, whereas prodomain cleavage sites are cleaved in an intradimeric manner within DISCs. Modeling indicated that sustained membrane-bound caspase-8 activity is followed by transient cytosolic activity, which can be interpreted as a molecular timer mechanism reflected by a limited lifetime of active caspase-8. The activation of caspase-8 by combined intra- and interdimeric cleavage ensures weak signaling at low concentrations of CD95L and strongly accelerated activation at higher ligand concentrations, thereby contributing to precise control of apoptosis.
This model is hosted on BioModels Database
and identified
by: BIOMD0000000525
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
2024-09-02 | BIOMD0000000525 | BioModels