LIVIVO - Search results -

Search results

Result 1 - 10 of total 29

Search options

Article ; Online: Trailblazing LIM kinases take the lead in collective tumor cell invasion.

Crighton, Diane / Olson, Michael F

Bioarchitecture

2011 Volume 1, Issue 1, Page(s) 5–8

Abstract: The spread of tumor cells from primary sites often occurs as associated cell collectives. In this form of invasion, the contribution of cells leading the way may differ from those that follow. By implication, proteins that regulate the actin cytoskeleton, ...

Abstract	The spread of tumor cells from primary sites often occurs as associated cell collectives. In this form of invasion, the contribution of cells leading the way may differ from those that follow. By implication, proteins that regulate the actin cytoskeleton, a major driver of cell motility, may have different roles depending on whether they are in leading or following cells. The LIM kinases 1 and 2 (LIMK) phosphorylate and inactivate the filamentous actin severing function of cofilin proteins. Using siRNA or pharmacological inhibitors, LIMK was found to be required in leading cells of collectively invading tumor cells, or in cancer-associated stromal fibroblasts, for effective extracellular matrix degradation that facilitates three-dimensional invasion. The decreased extracellular matrix degrading activities were associated with an inability to form the stable filamentous actin structures necessary to make matrix-degrading protrusive structures. However, LIMK was not required for cell motility or for path-following in associated collectives. These findings show that leading and following cells in collective invasion have different properties and indicate that targeting the activities in leading cells is sufficient to significantly inhibit tumor cell invasiveness.
Language	English
Publishing date	2011-08-08
Publishing country	United States
Document type	Journal Article
ISSN	1949-100X
ISSN (online)	1949-100X
DOI	10.4161/bioa.1.1.14628
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Modeling and imaging 3-dimensional collective cell invasion.

Scott, Rebecca W / Crighton, Diane / Olson, Michael F

Journal of visualized experiments : JoVE

2011 , Issue 58

Abstract: A defining characteristic of cancer malignancy is invasion and metastasis. In some cancers (e.g. glioma), local invasion into surrounding healthy tissue is the root cause of disease and death. For other cancers (e.g. breast, lung, etc.), it is the ... ...

Abstract	A defining characteristic of cancer malignancy is invasion and metastasis. In some cancers (e.g. glioma), local invasion into surrounding healthy tissue is the root cause of disease and death. For other cancers (e.g. breast, lung, etc.), it is the process of metastasis, in which tumor cells move from a primary tumor mass, colonize distal sites and ultimately contribute to organ failure, that eventually leads to morbidity and mortality. It has been estimated that invasion and metastasis are responsible for 90% of cancer deaths. As a result, there has been intense interest in identifying the molecular processes and critical protein mediators of invasion and metastasis for the purposes of improving diagnosis and treatment. A challenge for cancer scientists is to develop invasion assays that sufficiently resemble the in vivo situation to enable accurate disease modeling. Two-dimensional cell motility assays are only informative about one aspect of invasion and do not take into account extracellular matrix (ECM) protein remodeling which is also a critical element. Recently, research has refined our understanding of tumor cell invasion and revealed that individual cells may move by elongated or rounded modes. In addition, there has been greater appreciation of the contribution of collective invasion, in which cells invade in strands, sheets and clusters, particularly in highly differentiated tumors that maintain epithelial characteristics, to the spread of cancer. We present a refined method for examining the contributions of candidate proteins to collective invasion. In particular, by engineering separate pools of cells to express different fluorescent proteins, it is possible to molecularly dissect the activities and proteins required in leading cells versus those required in following cells. The use of RNAi provides the molecular tool to experimentally disassemble the processes involved in individual cell invasion as well as in different positions of collective invasion. In this procedure, mixtures of fluorescently-labeled cells are plated on the bottom of a Transwell insert previously filled with Matrigel ECM protein, then allowed to invade "upwards" through the filter and into the Matrigel. Reconstruction of z-series image stacks, obtained by confocal imaging, into three-dimensional representations allows for visualization of collectively invading strands and analysis of the representation of fluorescently-labeled cells in leading versus following positions.
MeSH term(s)	Animals ; Cell Culture Techniques/methods ; Cell Movement/physiology ; Collagen ; Drug Combinations ; Extracellular Matrix Proteins/metabolism ; Fluorescent Dyes/chemistry ; Humans ; Imaging, Three-Dimensional ; Laminin ; Neoplasm Invasiveness ; Neoplasms/chemistry ; Neoplasms/metabolism ; Neoplasms/pathology ; Proteoglycans
Chemical Substances	Drug Combinations ; Extracellular Matrix Proteins ; Fluorescent Dyes ; Laminin ; Proteoglycans ; matrigel (119978-18-6) ; Collagen (9007-34-5)
Language	English
Publishing date	2011-12-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/3525
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: p53 directly regulates the glycosidase FUCA1 to promote chemotherapy-induced cell death.

Baudot, Alice D / Crighton, Diane / O'Prey, Jim / Somers, Joanna / Sierra Gonzalez, Pablo / Ryan, Kevin M

Cell cycle (Georgetown, Tex.)

2016 Volume 15, Issue 17, Page(s) 2299–2308

Abstract: p53 is a central factor in tumor suppression as exemplified by its frequent loss in human cancer. p53 exerts its tumor suppressive effects in multiple ways, but the ability to invoke the eradication of damaged cells by programmed cell death is considered ...

Abstract	p53 is a central factor in tumor suppression as exemplified by its frequent loss in human cancer. p53 exerts its tumor suppressive effects in multiple ways, but the ability to invoke the eradication of damaged cells by programmed cell death is considered a key factor. The ways in which p53 promotes cell death can involve direct activation or engagement of the cell death machinery, or can be via indirect mechanisms, for example though regulation of ER stress and autophagy. We present here another level of control in p53-mediated tumor suppression by showing that p53 activates the glycosidase, FUCA1, a modulator of N-linked glycosylation. We show that p53 transcriptionally activates FUCA1 and that p53 modulates fucosidase activity via FUCA1 up-regulation. Importantly, we also report that chemotherapeutic drugs induce FUCA1 and fucosidase activity in a p53-dependent manner. In this context, while we found that over-expression of FUCA1 does not induce cell death, RNAi-mediated knockdown of endogenous FUCA1 significantly attenuates p53-dependent, chemotherapy-induced apoptotic death. In summary, these findings add an additional component to p53s tumor suppressive response and highlight another mechanism by which the tumor suppressor controls programmed cell death that could potentially be exploited for cancer therapy.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Cell Death/drug effects ; Cell Line, Tumor ; DNA Damage ; Humans ; Tumor Suppressor Protein p53/metabolism ; alpha-L-Fucosidase/genetics ; alpha-L-Fucosidase/metabolism
Chemical Substances	Antineoplastic Agents ; FUCA1 protein, human ; Tumor Suppressor Protein p53 ; alpha-L-Fucosidase (EC 3.2.1.51)
Language	English
Publishing date	2016-06-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2146183-1
ISSN	1551-4005 ; 1538-4101 ; 1554-8627
ISSN (online)	1551-4005
ISSN	1538-4101 ; 1554-8627
DOI	10.1080/15384101.2016.1191714
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5881: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Splicing DNA-damage responses to tumour cell death.

Crighton, Diane / Ryan, Kevin M

Biochimica et biophysica acta

2004 Volume 1705, Issue 1, Page(s) 3–15

Abstract: The ability of a tumour cell to evade programmed cell death (apoptosis) is crucial in the development of cancer. The process of apoptosis is complex and involves the careful interplay of a host of signalling molecules. Cellular stresses, such as DNA- ... ...

Abstract	The ability of a tumour cell to evade programmed cell death (apoptosis) is crucial in the development of cancer. The process of apoptosis is complex and involves the careful interplay of a host of signalling molecules. Cellular stresses, such as DNA-damage, can initiate apoptosis through multiple pathways, all of which eventually lead to eradication of damaged cells that may otherwise go on to form a tumour. Moreover, the relevance of this to combating cancer is very strong since several therapeutic agents used to treat malignant disease utilize the cells' apoptotic machinery. The purpose of this review is to provide an insight into what we know about how apoptosis is initiated by DNA-damaging agents, how pro- and anti-apoptotic signals converge in the execution of cell death, and how such mechanisms can be perturbed in cancer.
MeSH term(s)	Apoptosis/genetics ; Cell Cycle Proteins/genetics ; DNA Damage ; DNA-Binding Proteins/genetics ; E2F Transcription Factors ; Genes, Tumor Suppressor ; Humans ; JNK Mitogen-Activated Protein Kinases/genetics ; MAP Kinase Kinase 4 ; Mitogen-Activated Protein Kinase Kinases/genetics ; Neoplasms/genetics ; Neoplasms/physiopathology ; Oncogenes ; Signal Transduction ; Transcription Factors/genetics
Chemical Substances	Cell Cycle Proteins ; DNA-Binding Proteins ; E2F Transcription Factors ; Transcription Factors ; JNK Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; MAP Kinase Kinase 4 (EC 2.7.12.2) ; Mitogen-Activated Protein Kinase Kinases (EC 2.7.12.2)
Language	English
Publishing date	2004-12-10
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbcan.2004.09.001
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.247: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Do community demographics, environmental characteristics and access to care affect risks of developing ACOS and mortality in people with asthma?

To, Teresa / Zhu, Jingqin / Carlsten, Christopher / Larsen, Kristian / Ryckman, Kandace / Feldman, Laura Y / Crighton, Eric / Lougheed, M Diane / Licskai, Christopher / Villeneuve, Paul J / Su, Yushan / Sadatsafavi, Mohsen / Gershon, Andrea

The European respiratory journal

2017 Volume 50, Issue 3

MeSH term(s)	Adult ; Asthma/diagnosis ; Asthma/epidemiology ; Asthma/physiopathology ; Asthma/psychology ; Canada/epidemiology ; Comorbidity ; Demography ; Environmental Exposure/adverse effects ; Environmental Exposure/statistics & numerical data ; Female ; Health Services Accessibility/statistics & numerical data ; Humans ; Incidence ; Male ; Mortality ; Pulmonary Disease, Chronic Obstructive/diagnosis ; Pulmonary Disease, Chronic Obstructive/epidemiology ; Pulmonary Disease, Chronic Obstructive/physiopathology ; Pulmonary Disease, Chronic Obstructive/psychology ; Quality of Life ; Respiratory Function Tests/methods ; Risk Factors ; Symptom Flare Up
Language	English
Publishing date	2017-09-11
Publishing country	England
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	639359-7
ISSN	1399-3003 ; 0903-1936
ISSN (online)	1399-3003
ISSN	0903-1936
DOI	10.1183/13993003.00644-2017
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2322: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 292: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: DRAM links autophagy to p53 and programmed cell death.

Crighton, Diane / Wilkinson, Simon / Ryan, Kevin M

Autophagy

2007 Volume 3, Issue 1, Page(s) 72–74

Abstract: It is clear that changes in autophagy and autophagy regulators occur during tumor development and that this can have profound effects in certain tumor settings. The fact that p53, a key tumor suppressor mutated in approximately 50% of human cancers, has ... ...

Abstract	It is clear that changes in autophagy and autophagy regulators occur during tumor development and that this can have profound effects in certain tumor settings. The fact that p53, a key tumor suppressor mutated in approximately 50% of human cancers, has now also been shown to induce autophagy, has placed autophagy center stage in the minds of those interested in the development and treatment of malignant disease. p53 is a transcription factor that responds to cellular stress and prevents the propagation of cells which may otherwise form a tumor. The recent discovery, therefore, of DRAM (damage-regulated autophagy modulator) as a new p53 target which modulates autophagy is a major step forward in understanding how p53 controls autophagy and how this relates to tumor suppression. DRAM is a lysosomal protein that is not only critical for the ability of p53 to induce autophagy, but also for p53's ability to induce programmed cell death--a facet of p53 considered central to its tumor-suppressive effects. The fact that DRAM is also inactivated in certain cancers underscores its importance and highlights the possibility that autophagy may have a more profound role in cancer than was first believed.
MeSH term(s)	Apoptosis/physiology ; Autophagy/physiology ; Humans ; Membrane Proteins ; Models, Biological ; Proteins/physiology ; Tumor Suppressor Protein p53/physiology
Chemical Substances	DRAM1 protein, human ; Membrane Proteins ; Proteins ; Tumor Suppressor Protein p53
Language	English
Publishing date	2007-01-28
Publishing country	United States
Document type	Comment ; Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2454135-7
ISSN	1554-8635 ; 1554-8627
ISSN (online)	1554-8635
ISSN	1554-8627
DOI	10.4161/auto.3438
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 6741: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: Modeling and imaging 3-dimensional collective cell invasion

Scott, Rebecca W / Crighton, Diane / Olson, Michael F

Journal of visualized experiments. 2011 Dec. 07, , no. 58

2011

Abstract: A defining characteristic of cancer malignancy is invasion and metastasis 1. In some cancers (e.g. glioma 2), local invasion into surrounding healthy tissue is the root cause of disease and death. For other cancers (e.g. breast, lung, etc.), it is the ... ...

Abstract	A defining characteristic of cancer malignancy is invasion and metastasis 1. In some cancers (e.g. glioma 2), local invasion into surrounding healthy tissue is the root cause of disease and death. For other cancers (e.g. breast, lung, etc.), it is the process of metastasis, in which tumor cells move from a primary tumor mass, colonize distal sites and ultimately contribute to organ failure, that eventually leads to morbidity and mortality 3. It has been estimated that invasion and metastasis are responsible for 90% of cancer deaths 4. As a result, there has been intense interest in identifying the molecular processes and critical protein mediators of invasion and metastasis for the purposes of improving diagnosis and treatment 5. A challenge for cancer scientists is to develop invasion assays that sufficiently resemble the in vivo situation to enable accurate disease modeling 6. Two-dimensional cell motility assays are only informative about one aspect of invasion and do not take into account extracellular matrix (ECM) protein remodeling which is also a critical element. Recently, research has refined our understanding of tumor cell invasion and revealed that individual cells may move by elongated or rounded modes 7. In addition, there has been greater appreciation of the contribution of collective invasion, in which cells invade in strands, sheets and clusters, particularly in highly differentiated tumors that maintain epithelial characteristics, to the spread of cancer 8. We present a refined method 9 for examining the contributions of candidate proteins to collective invasion 10. In particular, by engineering separate pools of cells to express different fluorescent proteins, it is possible to molecularly dissect the activities and proteins required in leading cells versus those required in following cells. The use of RNAi provides the molecular tool to experimentally disassemble the processes involved in individual cell invasion as well as in different positions of collective invasion. In this procedure, mixtures of fluorescently-labeled cells are plated on the bottom of a Transwell insert previously filled with Matrigel ECM protein, then allowed to invade "upwards" through the filter and into the Matrigel. Reconstruction of z-series image stacks, obtained by confocal imaging, into three-dimensional representations allows for visualization of collectively invading strands and analysis of the representation of fluorescently-labeled cells in leading versus following positions.
Keywords	RNA interference ; breasts ; cell movement ; confocal microscopy ; death ; engineering ; epithelium ; extracellular matrix ; fluorescent proteins ; glioma ; image analysis ; lungs ; metastasis ; models ; morbidity ; mortality ; neoplasm cells
Language	English
Dates of publication	2011-1207
Size	p. e3525.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/3525
Database	NAL-Catalogue (AGRICOLA)

Order via subito

Article ; Online: Extracellular adenosine sensing-a metabolic cell death priming mechanism downstream of p53.

Long, Jaclyn S / Crighton, Diane / O'Prey, James / Mackay, Gillian / Zheng, Liang / Palmer, Timothy M / Gottlieb, Eyal / Ryan, Kevin M

Molecular cell

2013 Volume 50, Issue 3, Page(s) 394–406

Abstract: Tumor cells undergo changes in metabolism to meet their energetic and anabolic needs. It is conceivable that mechanisms exist to sense these changes and link them to pathways that eradicate cells primed for cancer development. We report that the tumor ... ...

Abstract	Tumor cells undergo changes in metabolism to meet their energetic and anabolic needs. It is conceivable that mechanisms exist to sense these changes and link them to pathways that eradicate cells primed for cancer development. We report that the tumor suppressor p53 activates a cell death priming mechanism that senses extracellular adenosine. Adenosine, the backbone of ATP, accumulates under conditions of cellular stress or altered metabolism. We show that its receptor, A2B, is upregulated by p53. A2B expression has little effect on cell viability, but ligand engagement activates a caspase- and Puma-dependent apoptotic response involving downregulation of antiapoptotic Bcl-2 proteins. Stimulation of A2B also significantly enhances cell death mediated by p53 and upon accumulation of endogenous adenosine following chemotherapeutic drug treatment and exposure to hypoxia. Since extracellular adenosine also accumulates within many solid tumors, this distinct p53 function links programmed cell death to both a cancer- and therapy-associated metabolic change.
MeSH term(s)	Adenosine/genetics ; Adenosine/metabolism ; Animals ; Apoptosis/genetics ; Apoptosis Regulatory Proteins/genetics ; Apoptosis Regulatory Proteins/metabolism ; Caspases/genetics ; Caspases/metabolism ; Cell Death/genetics ; Cell Line, Tumor ; Cell Survival/genetics ; Down-Regulation/genetics ; HCT116 Cells ; Humans ; Hypoxia/genetics ; Hypoxia/metabolism ; Mice ; Mice, Inbred C57BL ; Proto-Oncogene Proteins c-bcl-2/genetics ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Receptor, Adenosine A2B/genetics ; Receptor, Adenosine A2B/metabolism ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism ; Up-Regulation/genetics
Chemical Substances	Apoptosis Regulatory Proteins ; Proto-Oncogene Proteins c-bcl-2 ; Receptor, Adenosine A2B ; Tumor Suppressor Protein p53 ; Caspases (EC 3.4.22.-) ; Adenosine (K72T3FS567)
Language	English
Publishing date	2013-04-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2013.03.016
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5055: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Discovery, Development, and SAR of Aminothiazoles as LIMK Inhibitors with Cellular Anti-Invasive Properties.

Charles, Mark D / Brookfield, Joanna L / Ekwuru, Tennyson C / Stockley, Martin / Dunn, John / Riddick, Michelle / Hammonds, Tim / Trivier, Elisabeth / Greenland, Gavin / Wong, Ai Ching / Cheasty, Anne / Boyd, Susan / Crighton, Diane / Olson, Michael F

Journal of medicinal chemistry

2015 Volume 58, Issue 20, Page(s) 8309–8313

Abstract: As part of a program to develop a small molecule inhibitor of LIMK, a series of aminothiazole inhibitors were discovered by high throughput screening. Scaffold hopping and subsequent SAR directed development led to a series of low nanomolar inhibitors of ...

Abstract	As part of a program to develop a small molecule inhibitor of LIMK, a series of aminothiazole inhibitors were discovered by high throughput screening. Scaffold hopping and subsequent SAR directed development led to a series of low nanomolar inhibitors of LIMK1 and LIMK2 that also inhibited the direct biomarker p-cofilin in cells and inhibited the invasion of MDA MB-231-luc cells in a matrigel inverse invasion assay.
MeSH term(s)	Actin Depolymerizing Factors/metabolism ; Animals ; Biotransformation ; Drug Design ; Enzyme Inhibitors/chemical synthesis ; Enzyme Inhibitors/pharmacology ; High-Throughput Screening Assays ; Humans ; Lim Kinases/antagonists & inhibitors ; Microsomes, Liver/metabolism ; Neoplasm Invasiveness ; Structure-Activity Relationship ; Thiazoles/chemical synthesis ; Thiazoles/pharmacology
Chemical Substances	Actin Depolymerizing Factors ; Enzyme Inhibitors ; Thiazoles ; LIMK1 protein, human (EC 2.7.11.1) ; LIMK2 protein, human (EC 2.7.11.1) ; Lim Kinases (EC 2.7.11.1)
Language	English
Publishing date	2015-09-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/acs.jmedchem.5b01242
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.B 151: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MB 1: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Activation of p73 and induction of Noxa by DNA damage requires NF-kappa B.

Martin, Angel G / Trama, Jason / Crighton, Diane / Ryan, Kevin M / Fearnhead, Howard O

Aging

2009 Volume 1, Issue 3, Page(s) 335–349

Abstract: Although the transcription factor NF-kappaB is most clearly linked to the inhibition of extrinsic apoptotic signals such as TNFalpha by upregulating known anti-apoptotic genes, NF-kappaB has also been proposed to be required for p53-induced apoptosis in ... ...

Abstract	Although the transcription factor NF-kappaB is most clearly linked to the inhibition of extrinsic apoptotic signals such as TNFalpha by upregulating known anti-apoptotic genes, NF-kappaB has also been proposed to be required for p53-induced apoptosis in transformed cells. However, the involvement of NF-kappaB in this process is poorly understood. Here we investigate this mechanism and show that in transformed MEFs lacking NF-kappaB (p65-null cells) genotoxin-induced cytochrome c release is compromised. To further address how NF-kappaB contributes to apoptosis, gene profiling by microarray analysis of MEFs was performed, revealing that NF-kappaB is required for expression of Noxa, a pro-apoptotic BH3-only protein that is induced by genotoxins and that triggers cytochrome c release. Moreover, we find that in the absence of NF-kappaB, genotoxin treatment cannot induce Noxa mRNA expression. Noxa expression had been shown to be regulated directly by genes of the p53 family, like p73 and p63, following genotoxin treatment. Here we show that p73 is activated after genotoxin treatment only in the presence of NF-kappaB and that p73 induces Noxa gene expression through the p53 element in the promoter. Together our data provides an explanation for how loss of NF-kappaB abrogates genotoxin-induced apoptosis.
MeSH term(s)	Animals ; Antineoplastic Agents, Phytogenic/pharmacology ; Apoptosis ; Cell Line ; Cytochromes c/metabolism ; DNA Damage ; DNA-Binding Proteins/metabolism ; Etoposide/pharmacology ; Gene Expression Profiling ; Gene Expression Regulation, Enzymologic/drug effects ; Humans ; Metabolic Networks and Pathways/drug effects ; Mice ; Nuclear Proteins/metabolism ; Promoter Regions, Genetic ; Proto-Oncogene Proteins c-bcl-2/biosynthesis ; Proto-Oncogene Proteins c-bcl-2/genetics ; Transcription Factor RelA/physiology ; Transcriptional Activation ; Tumor Protein p73 ; Tumor Suppressor Proteins/metabolism
Chemical Substances	Antineoplastic Agents, Phytogenic ; DNA-Binding Proteins ; Nuclear Proteins ; Pmaip1 protein, mouse ; Proto-Oncogene Proteins c-bcl-2 ; Rela protein, mouse ; TP73 protein, human ; Transcription Factor RelA ; Trp73 protein, mouse ; Tumor Protein p73 ; Tumor Suppressor Proteins ; Etoposide (6PLQ3CP4P3) ; Cytochromes c (9007-43-6)
Language	English
Publishing date	2009-02-18
Publishing country	United States
Document type	Journal Article
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.100026
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED