Jdp2 downregulates Trp53 transcription to promote leukaemogenesis in the context of Trp53 heterozygosity

L van der Weyden, A G Rust, R E McIntyre, C D Robles-Espinoza, M del Castillo Velasco-Herrera, R Strogantsev, A C Ferguson-Smith, S McCarthy, T M Keane, M J Arends, D J Adams

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)397-402
Number of pages6
JournalOncogene
Volume32
Issue number3
DOIs
Publication statusPublished - 17 Jan 2013

Keywords

  • Animals
  • Cell Transformation, Neoplastic
  • Down-Regulation
  • HEK293 Cells
  • Heterozygote
  • Humans
  • Leukemia
  • Lymphoma
  • Mice
  • NIH 3T3 Cells
  • Repressor Proteins
  • Transcription, Genetic
  • Tumor Suppressor Protein p53

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