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

Oncogene. 2013 Jan 17;32(3):397-402. doi: 10.1038/onc.2012.56. Epub 2012 Feb 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Jundp2 protein, mouse
  • Repressor Proteins
  • Tumor Suppressor Protein p53