title: Sensitisation of c-MYC-induced B-lymphoma cells to apoptosis by ATF2.
abstract: Transcription factors ATF2 (activating transcription factor 2) and ATF7 (activating transcription factor 7) are highly homologous members of the activator protein 1 (AP-1) family. Their activities are growth factor and stress stimulated and they strictly require phosphorylation by mitogen-activated protein (MAP) kinases for their transcriptional functions. In samples of human B-cell lymphomas as well as Eμ-Myc-driven mouse B-cell lymphomas, we find that ATF2 as well as MAP kinase c-Jun N-terminal kinase (JNK) are significantly up-regulated compared with normal human B-cell lines and mouse B cells, respectively. The B cell-specific deletion of ATF2 and ATF7 in mice results in significantly accelerated onset of Eμ-Myc-induced lymphoma. In addition, loss of ATF2/7 desensitises Eμ-Myc lymphoma cells to spontaneous as well as stress-induced apoptosis. Our results therefore suggest that c-MYC induces stress-mediated activation of ATF2 and ATF7 and that these transcription factors regulate apoptosis in response to oncogenic transformation of B cells.
authors: Department of Cell Regulation, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.
authors: J
authors: J
authors: Walczynski
authors: Department of Cell Regulation, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.
authors: S
authors: S
authors: Lyons
authors: Department of Cell Regulation, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.
authors: N
authors: N
authors: Jones
authors: Department of Cell Regulation, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.
authors: W
authors: W
authors: Breitwieser
mesh_terms: D051698:Activating Transcription Factor 2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051700:Activating Transcription Factor 3 / Q000096:biosynthesis; D051696:Activating Transcription Factors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D016393:Lymphoma, B-Cell / Q000473:pathology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D051379:Mice; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D015854:Up-Regulation
chemical_list: C497105:ATF2 protein, human; C490449:ATF3 protein, human; C427752:ATF7 protein, human; D051698:Activating Transcription Factor 2; D051700:Activating Transcription Factor 3; D051696:Activating Transcription Factors; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D004317:Doxorubicin; D048670:MAP Kinase Kinase 4; D053148:Caspase 3