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

18 Scopus citations

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 (US)
Pages (from-to)397-402
Number of pages6
JournalOncogene
Volume32
Issue number3
DOIs
StatePublished - Jan 17 2013
Externally publishedYes

Keywords

  • Jdp2
  • heterozygosity
  • lymphoma
  • mice
  • p53
  • transposon

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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