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Apolipoprotein A-1 is a negative target of v-Jun overexpression
1Department of Microbiology and Immunology, Eastern Virginia Medical School, Norfolk 23501, USA.
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.
Insights
The v-Jun oncogene downregulates apolipoprotein A-1 expression by affecting promoter activity, potentially impacting cholesterol metabolism. This regulation differs from c-Jun
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- The Jun oncogene regulates cell proliferation and differentiation by binding to gene regulatory regions.
- Understanding oncogene-induced gene expression changes is crucial for cancer research.
Purpose of the Study:
- To identify genes downregulated by v-Jun overexpression.
- To investigate the mechanism of v-Jun-mediated gene regulation.
- To explore the relationship between v-Jun, apolipoprotein A-1, and cholesterol metabolism.
Main Methods:
- Gene isolation and characterization via homology searches.
- RNA half-life analysis.
- Reporter gene assays using promoter fragments.
- Oncogene overexpression in chicken embryo fibroblasts (CEF).
Main Results:
- A gene downregulated by v-Jun, but not c-Jun, was identified as chicken apolipoprotein A-1 (ApoA-1).
- v-Jun downregulates ApoA-1 at the promoter activity level, not via RNA stability.
- Myc and v-Src oncogenes also downregulated ApoA-1 expression in CEF.
Conclusions:
- v-Jun directly represses apolipoprotein A-1 gene transcription.
- Altered apolipoprotein A-1 levels due to v-Jun may affect cholesterol metabolism.
- v-Jun oncogene exhibits distinct regulatory effects compared to c-Jun.