Journal
ONCOGENE
Volume 32, Issue 3, Pages 397-402Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2012.56
Keywords
p53; Jdp2; transposon; heterozygosity; lymphoma; mice
Funding
- Cancer Research UK
- Wellcome Trust
- Kay Kendall Leukaemia Fund
- Consejo Nacional de Ciencia y Tecnologia (CONACYT)
- MRC [G0800024] Funding Source: UKRI
- Cancer Research UK [14356, 13031] Funding Source: researchfish
- Medical Research Council [G0800024] Funding Source: researchfish
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We performed a genetic screen in mice to identify candidate genes that are associated with leukaemogenesis in the context of Trp53 heterozygosity. To do this we generated Trp53 heterozygous mice carrying the T2/Onc transposon and SB11 transposase alleles to allow transposon-mediated insertional mutagenesis to occur. From the resulting leukaemias/lymphomas that developed in these mice, we identified nine loci that are potentially associated with tumour formation in the context of Trp53 heterozygosity, including AB041803 and the Jun dimerization protein 2 (Jdp2). We show that Jdp2 transcriptionally regulates the Trp53 promoter, via an atypical AP-1 site, and that Jdp2 expression negatively regulates Trp53 expression levels. This study is the first to identify a genetic mechanism for tumour formation in the context of Trp53 heterozygosity. Oncogene (2013) 32, 397-402; doi:10.1038/onc.2012.56; published online 27 February 2012
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