Apolipoprotein A-1 is a negative target of v-Jun overexpression.
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.
Hadman
M
M
Department of Microbiology and Immunology, Eastern Virginia Medical School, Norfolk 23501, USA.
Lin
W
W
Bush
L
L
Bos
T J
TJ
D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001483:Base Sequence; D002642:Chick Embryo; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D015536:Down-Regulation; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D016758:Genes, jun; D008969:Molecular Sequence Data; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid
D016632:Apolipoprotein A-I; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D004247:DNA