학술논문
Jdp2 downregulates Trp53 transcription to promote leukaemogenesis in the context of Trp53 heterozygosity.
Document Type
Article
Author
Source
Subject
*GENETIC transcription
*PROMOTERS (Genetics)
*HETEROZYGOSITY
*GENE expression
*TRANSPOSASE genetics
*DIMERIZATION
*LABORATORY mice
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Language
ISSN
0950-9232
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. [ABSTRACT FROM AUTHOR]