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Interferons and oncogenes in the control of cell growth and differentiation: working hypothesis and experimental
N Mechti1, C Bisbal, J P Leonetti
1UA CNRS 1191, Université de Montpellier II, France.
Abstract:
This short review summarizes available evidence for (i) growth regulatory properties of exogenous as well as recently described autocrine IFNs, (ii) down-regulation of cellular oncogene expression with emphasis on c-myc and (iii) the possible involvement of the IFN-regulated 2-5A pathway at these levels. Initially described as a part of the IFN-induced antiviral mechanism, this double-stranded RNA-activated pathway leads to the preferential degradation of viral mRNAs in IFN-treated virus-infected cells probably through localized activation at the site of virus replication. Such mechanisms could be involved in the regulation of the stability of rapidly turning over mRNAs as for instance c-myc mRNA in IFN-treated cells. Whatever the elegance of the concept, however, experimental evidence is essentially circumstantial; tools developed in our group to strengthen the demonstration are briefly described.
Insights
This review explores how Interferons (IFNs) regulate cell growth and oncogene expression, specifically c-myc. It examines the role of the 2-5A pathway in these processes, suggesting potential mechanisms for mRNA stability regulation.
Area of Science:
- Molecular Biology
- Cell Biology
- Immunology
Background:
- Interferons (IFNs) are known for their antiviral properties.
- The 2-5A pathway, activated by double-stranded RNA, is a key component of the IFN-induced antiviral response.
- Oncogenes like c-myc play crucial roles in cell growth regulation.
Purpose of the Study:
- To review evidence on the growth-regulatory properties of IFNs (exogenous and autocrine).
- To summarize the down-regulation of cellular oncogene expression, particularly c-myc, by IFNs.
- To investigate the potential involvement of the IFN-regulated 2-5A pathway in these regulatory mechanisms.
Main Methods:
- Literature review of existing evidence.
- Discussion of the proposed role of the 2-5A pathway in mRNA degradation.
- Brief description of novel tools developed to strengthen experimental evidence.
Main Results:
- IFNs exhibit growth-regulatory properties.
- IFNs can down-regulate the expression of oncogenes such as c-myc.
- The 2-5A pathway is implicated in the regulation of mRNA stability, including c-myc mRNA.
Conclusions:
- The 2-5A pathway may contribute to the regulation of c-myc mRNA stability in IFN-treated cells.
- While the concept is elegant, current experimental evidence is largely circumstantial.
- Further research using developed tools is needed to solidify these findings.