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2-Aminopurine selectively inhibits the induction of beta-interferon, c-fos, and c-myc gene expression
K Zinn1, A Keller, L A Whittemore
1Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.
Abstract:
The protein kinase inhibitor 2-aminopurine (2AP) blocks the induction of the human beta-interferon gene by virus or poly(I)-poly(C) at the level of transcription. This inhibition is specific, since 2AP does not inhibit induction of either the hsp70 heat-shock gene by high temperature or the metallothionein gene by cadmium or dexamethasone. However, 2AP does block the induction of the c-fos and c-myc proto-oncogenes by serum growth factors or virus, suggesting that a protein kinase may be involved in the regulation of these genes, as well as of the beta-interferon gene. However, different factors must be required for the induction of these three genes, since they are not coordinately regulated by the same inducers in most of the cell lines examined.
Insights
The protein kinase inhibitor 2-aminopurine (2AP) specifically blocks beta-interferon gene induction. This suggests a protein kinase regulates beta-interferon, c-fos, and c-myc genes, but they require different induction factors.
Area of Science:
- Molecular Biology
- Gene Regulation
- Biochemistry
Background:
- The induction of the human beta-interferon gene is a critical antiviral response.
- Understanding the regulatory mechanisms of gene induction is essential for cellular defense and disease research.
Purpose of the Study:
- To investigate the role of protein kinases in the transcriptional regulation of the human beta-interferon gene.
- To determine if protein kinases are involved in the induction of other genes, such as proto-oncogenes.
Main Methods:
- Utilized 2-aminopurine (2AP), a specific protein kinase inhibitor.
- Examined the effect of 2AP on the induction of the beta-interferon gene by viral stimuli (virus or poly(I)-poly(C)).
- Assessed the specificity of 2AP inhibition by testing its effects on other inducible genes (hsp70, metallothionein, c-fos, c-myc).
Main Results:
- 2-aminopurine (2AP) specifically inhibited the transcriptional induction of the human beta-interferon gene.
- 2AP did not inhibit the induction of heat-shock or metallothionein genes, demonstrating specificity.
- 2AP blocked the induction of c-fos and c-myc proto-oncogenes by growth factors or virus.
Conclusions:
- A protein kinase appears to be involved in the transcriptional regulation of the beta-interferon gene.
- Protein kinases may also regulate the induction of c-fos and c-myc proto-oncogenes.
- Different factors are required for the induction of beta-interferon, c-fos, and c-myc genes, as they are not coordinately regulated.