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- Title
Jdp2 downregulates Trp53 transcription to promote leukaemogenesis in the context of Trp53 heterozygosity.
- Authors
van der Weyden, L; Rust, A G; McIntyre, R E; Robles-Espinoza, C D; del Castillo Velasco-Herrera, M; Strogantsev, R; Ferguson-Smith, A C; McCarthy, S; Keane, T M; Arends, M J; Adams, D J
- Abstract
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.
- Subjects
GENETIC transcription; PROMOTERS (Genetics); HETEROZYGOSITY; GENE expression; TRANSPOSASE genetics; DIMERIZATION; LABORATORY mice
- Publication
Oncogene, 2013, Vol 32, Issue 3, p397
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/onc.2012.56