Abstract
Suppression of c-Myc is likely to induce cellular senescence in many tumors with unclear mechanisms. A proteomics survey indicated that high levels of BCL2-associated athanogene 2 (BAG2) were found in response to c-Myc repression in TRE293 cells. This observation led to the investigation into the role of BAG2 in c-Myc-induced senescence. The association of the c-Myc/SP1 complex with the BAG2 promoter verified the role of c-Myc/SP1 in regulating BAG2 transcription. Furthermore, high levels of BAG2 were found to induce p21(CIP1)-dependent senescence and subsequent carcinogenetic arrest, suggesting its possible role as an indirect activator of the p21(CIP1) pathway.
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blotting, Western
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Cell Proliferation
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Cellular Senescence*
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Chromatin Immunoprecipitation
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Colonic Neoplasms / genetics
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Colonic Neoplasms / metabolism
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Colonic Neoplasms / pathology
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Cyclin-Dependent Kinase Inhibitor p21 / genetics
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Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
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Electrophoretic Mobility Shift Assay
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Fluorescent Antibody Technique
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Humans
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Immunoenzyme Techniques
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Immunoprecipitation
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Luciferases / metabolism
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Mice
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Mice, Nude
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Molecular Chaperones / genetics*
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Molecular Chaperones / metabolism
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Promoter Regions, Genetic / genetics
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Proto-Oncogene Proteins c-myc / antagonists & inhibitors
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Proto-Oncogene Proteins c-myc / genetics
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Proto-Oncogene Proteins c-myc / metabolism*
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RNA, Messenger / genetics
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RNA, Small Interfering / genetics
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Real-Time Polymerase Chain Reaction
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Sp1 Transcription Factor / genetics
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Sp1 Transcription Factor / metabolism
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Spectrometry, Mass, Electrospray Ionization
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Transcription, Genetic*
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Tumor Cells, Cultured
Substances
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BAG2 protein, human
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CDKN1A protein, human
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Cyclin-Dependent Kinase Inhibitor p21
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Molecular Chaperones
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Proto-Oncogene Proteins c-myc
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RNA, Messenger
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RNA, Small Interfering
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Sp1 Transcription Factor
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Luciferases