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rdf:type |
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lifeskim:mentions |
umls-concept:C0079904,
umls-concept:C0109317,
umls-concept:C0752312,
umls-concept:C1150579,
umls-concept:C1333340,
umls-concept:C1366882,
umls-concept:C1370600,
umls-concept:C1414928,
umls-concept:C1522790,
umls-concept:C1705767,
umls-concept:C1705791
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pubmed:issue |
13
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pubmed:dateCreated |
2005-3-28
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pubmed:abstractText |
NF-kappaB has been well documented to play a critical role in signaling cell stress reactions. The extracellular signal-regulated kinase (ERK) regulates cell proliferation and survival. GADD45beta is a primary cell cycle element responsive to NF-kappaB activation in anti-apoptotic responses. The present study provides evidence demonstrating that NK-kappaB, ERK and GADD45beta are co-activated by ionizing radiation (IR) in a pattern of mutually dependence to increase cell survival. Stress conditions generated in human breast cancer MCF-7 cells by the administration of a single exposure of 5 Gy IR resulted in the activation of ERK but not p38 or JNK, along with an enhancement of the NF-kappaB transactivation and GADD45beta expression. Overexpression of dominant negative Erk (DN-Erk) or pre-exposure to ERK inhibitor PD98059 inhibited NF-kappaB. Transfection of dominant negative mutant IkappaB that blocks NF-kappaB nuclear translocation, inhibited ERK activity and GADD45beta expression and increased cell radiosensitivity. Interaction of p65 and ERK was visualized in living MCF-7 cells by bimolecular fluorescence complementation analysis. Antisense inhibition of GADD45beta strikingly blocked IR-induced NF-kappaB and ERK but not p38 and JNK. Overall, these results demonstrate a possibility that NF-kappaB, ERK, and GADD45beta are able to coordinate in a loop-like signaling network to defend cells against the cytotoxicity induced by ionizing radiation.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/Flavonoids,
http://linkedlifedata.com/resource/pubmed/chemical/GADD45B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/PD 98059,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
12593-601
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15642734-Active Transport, Cell Nucleus,
pubmed-meshheading:15642734-Antigens, Differentiation,
pubmed-meshheading:15642734-Apoptosis,
pubmed-meshheading:15642734-Cell Line, Tumor,
pubmed-meshheading:15642734-Cell Nucleus,
pubmed-meshheading:15642734-Cell Proliferation,
pubmed-meshheading:15642734-Cell Survival,
pubmed-meshheading:15642734-Dose-Response Relationship, Drug,
pubmed-meshheading:15642734-Enzyme Activation,
pubmed-meshheading:15642734-Enzyme Inhibitors,
pubmed-meshheading:15642734-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:15642734-Flavonoids,
pubmed-meshheading:15642734-Genes, Dominant,
pubmed-meshheading:15642734-Genetic Complementation Test,
pubmed-meshheading:15642734-Humans,
pubmed-meshheading:15642734-I-kappa B Proteins,
pubmed-meshheading:15642734-Immunoblotting,
pubmed-meshheading:15642734-NF-kappa B,
pubmed-meshheading:15642734-Oligonucleotides, Antisense,
pubmed-meshheading:15642734-Plasmids,
pubmed-meshheading:15642734-Radiation, Ionizing,
pubmed-meshheading:15642734-Spectrometry, Fluorescence,
pubmed-meshheading:15642734-Spectrophotometry, Infrared,
pubmed-meshheading:15642734-Time Factors,
pubmed-meshheading:15642734-Transcriptional Activation,
pubmed-meshheading:15642734-Transfection,
pubmed-meshheading:15642734-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2005
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pubmed:articleTitle |
Co-activation of ERK, NF-kappaB, and GADD45beta in response to ionizing radiation.
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pubmed:affiliation |
Division of Radiation Oncology, Beckman Research Institute and City of Hope National Medical Center, Duarte, California 91010, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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