Interaction between cyclooxygenase-2 and caspase-3 abolishes the cleavage of RNA-binding protein HuR and promotes drug resistance in oral squamous cell carcinoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE79477 | GEO | 2017/02/14
SECONDARY ACCESSION(S): PRJNA315952
REPOSITORIES: GEO
Similar Datasets
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
Project description:Kallenberger2014 - CD95L induced apoptosis initiated by caspase-8, wild-type 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: BIOMD0000000526
.
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 | BIOMD0000000526 | BioModels
Project description:This is the standard model described in the article:
Systems analysis of effector caspase activation and its control by X-linked inhibitor of apoptosis protein.
Rehm M, Huber HJ, Dussmann H, Prehn JH.
EMBO J. 2006 Sep 20;25(18):4338-49. Epub 2006 Aug 24.
PMID:16932741, doi:10.1038/sj.emboj.7601295;
Abstract:
Activation of effector caspases is a final step during apoptosis. Single-cell imaging studies have demonstrated that this process may occur as a rapid, all-or-none response, triggering a complete substrate cleavage within 15 min. Based on biochemical data from HeLa cells, we have developed a computational model of apoptosome-dependent caspase activation that was sufficient to remodel the rapid kinetics of effector caspase activation observed in vivo. Sensitivity analyses predicted a critical role for caspase-3-dependent feedback signalling and the X-linked-inhibitor-of-apoptosis-protein (XIAP), but a less prominent role for the XIAP antagonist Smac. Single-cell experiments employing a caspase fluorescence resonance energy transfer substrate verified these model predictions qualitatively and quantitatively. XIAP was predicted to control this all-or-none response, with concentrations as high as 0.15 microM enabling, but concentrations >0.30 microM significantly blocking substrate cleavage. Overexpression of XIAP within these threshold concentrations produced cells showing slow effector caspase activation and submaximal substrate cleavage. Our study supports the hypothesis that high levels of XIAP control caspase activation and substrate cleavage, and may promote apoptosis resistance and sublethal caspase activation in vivo.
This model is slightly altered from the description in the article. Cytochrome C and SMAC release from the mitochondrion is modelled as simple first order kinetics, giving the same form as the (integrated) equations in the supplement of the article. The apoptosome formation is modelled equally - and independent of the Cytochrome C release. The speed is either limited by the Apaf1 or ProCaspase9 concentration, whichever is higher, symbolised via the parameter with the ID apolim.
Also, once the substrate concentration falls below 1 percent, the event Production_Breakdown is triggered, leading to a breakdown of XIAP and procaspase3 production and turning off of the enhanced/proteosomal degradation (degradation rate for reactions 38,39,40,43,44,46,48,50,51 changes from 0.0347 to 0.0058).
Originally created by libAntimony v1.3 (using libSBML 3.4.1)
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2012 The BioModels.net Team.
For more information see the terms of use.
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2024-09-02 | BIOMD0000000256 | BioModels
Project description:We characterized the proteome of the auditory brainstem of a chick embryo on embryonic day 13, when apoptosis occurs in auditory nuclei. We identified caspase substrates by searching the peptidome for peptides C-terminal to caspase-typical cleavage sites.
2022-04-01 | PXD030697 | Pride
Project description:X-linked inhibitor of apoptosis (XIAP) is the most potent endogenous caspase inhibitor preventing cell death via caspase-9, -7 and -3 (initiator and executioner caspase pathways). Using short hairpin RNA (shRNA) against XIAP, stably expressed in a parent HCT116 human colon cancer cell line, a series of clones have been developed. XIAP mRNA levels were established by RT-PCR, the four X (XIAP knockdown) clonal cell lines show 82-93% reduction in XIAP mRNA when compared to the four L (luciferase control) cell lines. Immunoblot analysis showed a 67-89% reduction in XIAP protein in X cell lines compared to L. RNA was analysed by microarray and XIAP knockdown was confirmed in 7 probe sets, there was no significant compensation of other IAP family members. XIAP knockdown induced a 2-fold increase in the basal level of apoptosis without modification of caspase 3/7 activity. Finally, XIAP knockdown sensitises cells to radiotherapy by 20%, to recombinant TRAIL by a 3-fold factor, and to paclitaxel and docetaxel by >2 fold factor. Future work should focus on targeted agents such as rhTRAIL in combination with strategies to down regulate XIAP. XIAP antisense is now in clinical development in oncology.
2008-12-01 | GSE11618 | GEO
Project description:Purpose: The goal of this study is to understand the signaling pathway alteration in cancer cell line treated with TEAD palmitoylation inhibitor MGH-CP1, and to further validate TEAD inhibitor for specifity in TEAD-YAP interuption. Methods:Breast cancer cell line MDA-MB-231 was chosen to be treated with TEAD palmitoylation inhibitor MGH-CP1 at 10μM for 24 hours. Total RNA was isolated for the analysis. RNA samples were sent to Novogen for library construction, RNA sequencing and raw data process. Results: MGH-CP1 specifically blocks TEAD transcriptional activity compared with YAP/TAZ siRNA in MDA-MB-231 cells. Conclusions: Our study privides gene expression profiling evidence to validate our TEAD palmitoylation inhibitor MGH-CP1 as specific small molecule to block TEAD transcriptional activity. We report the application of next generation sequencing technology for high-throughput profiling of TEAD palmitoylation inhibitor MGH-CP1 in breast cancer cells.
2021-05-11 | GSE140396 | GEO
Project description:Primary objectives: The main primary objective is to assess levels of anthocyanins and their metabolites achieved in biomatrices from patients following a seven-day course of oral Mirtoselect. Specifically, the following detailed aims are to be achieved:
• To measure the levels of anthocyanins in normal and malignant colorectal tissues. • To compare concentrations of anthocyanins achieved in tissues after three different oral dose levels of Mirtoselect.• To assess the levels of anthocyanins and their metabolites in peripheral venous circulation, urine and stool.
Primary endpoints: Levels of anthocyanins and their metabolites achieved in colorectal tissue, urine and the perhipheral venous cirulation.
Levels of molecular biomarkers (including levels of oxidative DNA adduct M1dG, ii. levels of inducible COX-2, iii. levels of phosphorylated EGFR, iv. indicators of proliferation (e.g. Ki67), angiogenesis (e.g. CD 34) and apoptosis (e.g. caspase 3)).
| 2520418 | ecrin-mdr-crc
Project description:Background: The acquisition of drug resistance is one of the most malignant phenotypes of cancer. MicroRNAs (miRNAs) have been implicated in various types of cancers, but its role in taxane-resistance of prostate cancer remains poorly understood. Methods: In order to identify miRNAs related to taxane-resistance, miRNA profiling was performed using prostate cancer PC3 cells and paclitaxel-resistant PC3 cell lines established from PC3 cells. Microarray analysis of mRNA expression was also conducted to search for potential target genes of miRNA. The effects of ectopic expression of miRNA on cell growth, tubulin polymerization, drug sensitivity and apoptotic signaling pathway were investigated in a paclitaxel-resistant PC3 cell line. Results: The expression of miR-130a was down-regulated in all paclitaxel-resistant cell lines compared with parental PC3 cells. Based on mRNA microarray analysis, we identified SLAIN1 and CAV2 as potential target genes for miR-130a. Transfection with a miR-130a precursor into a paclitaxel-resistant cell line suppressed cell growth and increased the sensitivity to paclitaxel. Lastly, ectopic expression of miR-130a did not affect the polymerized tubulin level, but activated apoptotic signaling through activation of caspase-8. Conclusion: These results suggested that miR-130a may be involved in the paclitaxel-resistance and could be a therapeutic target for taxane-resistant prostate cancer. Human hormone-refractory prostate cancer PC3 cells were cultured in RPMI1640 medium supplemented with 10 % of fetal bovine serum, 100 units/ml of penicillin and 100 ug/ml of streptomycin. Paclitaxel-resistant PC3PR20, PC3PR70 and PC3PR200 cells, which respectively could proliferate in the presence of 20, 70 and 200 nM of paclitaxel (Sigma-Aldrich, St. Louis, MO, USA), were previously established from PC3 cells by a stepwise increase of paclitaxel in the culture medium (Kojima et al, 2010, Prostate 70: 1501-12).
2015-07-31 | E-GEOD-64012 | biostudies-arrayexpress