title: Jdp2 downregulates Trp53 transcription to promote leukaemogenesis in the context of Trp53 heterozygosity.
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.
authors.affiliation: Wellcome Trust Sanger Institute, Cambridge, UK.
authors.forename: L
authors.initials: L
authors.lastname: van der Weyden
authors.forename: A G
authors.initials: AG
authors.lastname: Rust
authors.forename: R E
authors.initials: RE
authors.lastname: McIntyre
authors.forename: C D
authors.initials: CD
authors.lastname: Robles-Espinoza
authors.forename: M
authors.initials: M
authors.lastname: del Castillo Velasco-Herrera
authors.forename: R
authors.initials: R
authors.lastname: Strogantsev
authors.forename: A C
authors.initials: AC
authors.lastname: Ferguson-Smith
authors.forename: S
authors.initials: S
authors.lastname: McCarthy
authors.forename: T M
authors.initials: TM
authors.lastname: Keane
authors.forename: M J
authors.initials: MJ
authors.lastname: Arends
authors.forename: D J
authors.initials: DJ
authors.lastname: Adams
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015536:Down-Regulation; D057809:HEK293 Cells; D006579:Heterozygote; D006801:Humans; D007938:Leukemia / Q000235:genetics* / Q000473:pathology*; D008223:Lymphoma / Q000235:genetics / Q000473:pathology; D051379:Mice; D041681:NIH 3T3 Cells; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C491386:Jundp2 protein, mouse; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53