Sensitisation of c-MYC-induced B-lymphoma cells to apoptosis by ATF2

• Published in: Oncogene Vol. 33; no. 8; pp. 1027 - 1036
• Main Authors: Walczynski, J, Lyons, S, Jones, N, Breitwieser, W
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20-02-2014; Nature Publishing Group
• Subjects: 631/208/200; 692/420/755; 692/699/67/1990/291/1621/1915; Activating transcription factor 2; Activating Transcription Factor 2 - genetics; Activating Transcription Factor 2 - metabolism; Activating Transcription Factor 2 - physiology; Activating Transcription Factor 3 - biosynthesis; Activating Transcription Factors - genetics; Activating Transcription Factors - metabolism; Activator protein 1; Animals; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; B-cell lymphoma; c-Jun protein; c-Myc protein; Care and treatment; Caspase 3 - metabolism; Cell Biology; Clonal deletion; Comparative analysis; Doxorubicin - pharmacology; Enzyme Activation; Genetic aspects; Genetic research; Human Genetics; Humans; Internal Medicine; JNK protein; Kinases; Lymphocytes B; Lymphoma; Lymphoma, B-Cell - pathology; Lymphomas; MAP kinase; MAP Kinase Kinase 4 - metabolism; Medicine; Medicine & Public Health; Mice; Myc protein; Oncology; original-article; Oxidative stress; Phosphorylation; Phosphotransferases; Physiological aspects; Proto-Oncogene Proteins c-jun - biosynthesis; Proto-Oncogene Proteins c-myc - physiology; Transcription factors; Up-Regulation; United Kingdom; United Kingdom > UK; B lymphoma; ATF2; apoptosis; ATF7; c-MYC; JNK
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2013.28

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.