Abstract
Embryonic stem (ES) cells contain a p53-dependent apoptosis mechanism to avoid the continued proliferation and differentiation of damaged cells. We show that mouse ES cells lacking Ets1 are deficient in their ability to undergo UV-induced apoptosis, similar to p53 null ES cells. In Ets1(-/-) ES cells, UV induction of the p53 regulated genes mdm2, perp, cyclin G and bax was decreased both at mRNA and protein levels. While p53 protein levels were unaltered in Ets1(-/-) cells, its ability to transactivate genes such as mdm2 and cyclin G was reduced. Furthermore, electrophoretic mobility shift assays and immunoprecipitations demonstrated that the presence of Ets1 was necessary for a CBP/p53 complex to be formed. Chromatin immunoprecipitations demonstrated that Ets1 was required for the formation of a stable p53-DNA complex under physiological conditions and activation of histone acetyltransferase activity. These data demonstrate that Ets1 is an essential component of a UV-responsive p53 transcriptional activation complex in ES cells and suggests that Ets1 may contribute to the specificity of p53-dependent gene transactivation in distinct cellular compartments.
MeSH terms
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Acetylation
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Acetyltransferases / metabolism
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Animals
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Apoptosis / physiology*
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Apoptosis / radiation effects
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CREB-Binding Protein
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Cell Compartmentation
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Cell Cycle / genetics
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Cell Cycle / radiation effects
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Cells, Cultured / cytology
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Cells, Cultured / metabolism
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Chromatin / metabolism
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Chromatin / radiation effects
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Cyclin G
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Cyclin G1
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Cyclins / biosynthesis
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Cyclins / genetics
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DNA / chemistry
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DNA / metabolism*
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Enzyme Activation
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Gene Expression Regulation / radiation effects
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Gene Targeting
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Genes, p53
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Histone Acetyltransferases
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Histones / metabolism
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Macromolecular Substances
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Membrane Proteins / biosynthesis
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Membrane Proteins / genetics
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Mice
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Nuclear Proteins / chemistry
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Nuclear Proteins / metabolism
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Protein Binding
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Protein Processing, Post-Translational
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Proto-Oncogene Protein c-ets-1
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins / deficiency
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / physiology*
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Proto-Oncogene Proteins c-bcl-2*
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Proto-Oncogene Proteins c-ets
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Proto-Oncogene Proteins c-mdm2
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Recombinant Fusion Proteins / physiology
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Saccharomyces cerevisiae Proteins*
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Stem Cells / cytology
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Stem Cells / metabolism
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Stem Cells / radiation effects*
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Trans-Activators / chemistry
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Trans-Activators / metabolism
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Transcription Factors / deficiency
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Transcription Factors / genetics
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Transcription Factors / physiology*
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Transcription, Genetic / physiology*
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Transcription, Genetic / radiation effects
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Transfection
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Tumor Suppressor Protein p53 / chemistry
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Tumor Suppressor Protein p53 / physiology*
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Ultraviolet Rays*
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bcl-2-Associated X Protein
Substances
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Bax protein, mouse
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CCNG1 protein, human
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Ccng1 protein, mouse
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Chromatin
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Cyclin G
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Cyclin G1
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Cyclins
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Ets1 protein, mouse
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Histones
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Macromolecular Substances
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Membrane Proteins
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Nuclear Proteins
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Perp protein, mouse
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Proto-Oncogene Protein c-ets-1
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Proto-Oncogene Proteins c-ets
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RNA, Messenger
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Recombinant Fusion Proteins
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Saccharomyces cerevisiae Proteins
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Trans-Activators
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Transcription Factors
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Tumor Suppressor Protein p53
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bcl-2-Associated X Protein
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DNA
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Acetyltransferases
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CREB-Binding Protein
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Crebbp protein, mouse
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Histone Acetyltransferases
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Mdm2 protein, mouse
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Proto-Oncogene Proteins c-mdm2