Ets1 is required for p53 transcriptional activity in UV-induced apoptosis in embryonic stem cells.
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.
Xu
Dakang
D
Centre for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Monash University, 246 Clayton, Clayton, Victoria 3168, Australia.
Wilson
Trevor J
TJ
Chan
David
D
De Luca
Elisabetta
E
Zhou
Jiong
J
Hertzog
Paul J
PJ
Kola
Ismail
I
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects; D050882:CREB-Binding Protein; D002451:Cell Compartmentation; D002453:Cell Cycle / Q000235:genetics / Q000528:radiation effects; D002478:Cells, Cultured / Q000166:cytology / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism / Q000528:radiation effects; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000528:radiation effects; D018390:Gene Targeting; D016158:Genes, p53; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D050783:Proto-Oncogene Proteins c-ets; D051736:Proto-Oncogene Proteins c-mdm2; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology* / Q000528:radiation effects; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000502:physiology*; D014466:Ultraviolet Rays; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; C534702:CCNG1 protein, human; C534703:Ccng1 protein, mouse; D002843:Chromatin; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins; C494042:Ets1 protein, mouse; D006657:Histones; D046911:Macromolecular Substances; D008565:Membrane Proteins; D009687:Nuclear Proteins; C406964:Perp protein, mouse; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D004247:DNA; D000123:Acetyltransferases; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D051548:Histone Acetyltransferases; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2