Apolipoprotein A-1 is a negative target of v-Jun overexpression

Abstract

The product of the Jun oncogene influences a variety of processes including cell proliferation and differentiation. Jun exerts its influence by binding to the promoter and enhancer regions of a number of different target genes resulting in their activation or repression. We describe here the isolation and characterization of a gene differentially downregulated upon overexpression of v-Jun but not c-Jun. DNA and amino acid homology search analysis revealed this gene to be identical to chicken apolipoprotein A-1, the major component of high density lipoprotein (HDL). The half life of apolipoprotein A-1 RNA remains constant in the presence or absence of v-Jun overexpression suggesting downregulation by v-Jun is at the level of promoter activity. Consistent with this hypothesis, apolipoprotein A-1 upstream promoter fragments active in normal and c-Jun expressing CEF are inactive in v-Jun transformed CEF. Analysis of expression of apolipoprotein A-1 in CEF overexpressing other oncogenes revealed a similar downregulation by Myc and v-Src but not c-Fos, v-Ha-Ras, c-Src or c-Ski. Our findings point to a potential regulatory affect on cholesterol metabolism by v-Jun, as a result of altered levels of apolipoprotein A-1 message expression.