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Induction of the mitogen-activated p70 S6 kinase by adenovirus E1A
R P de Groot1, G J Schouten, L de Wit
1Laboratory for Molecular Carcinogenesis, Sylvius Laboratories, University of Leiden, The Netherlands.
Abstract:
Adenovirus E1A proteins can transform primary cells in culture in conjunction with other oncogenes, such as E1B or activated ras. The modulation of various cell cycle regulators by E1A is thought to be involved in this transformation process. In this paper we show that E1A enhances the expression of the mitogen-inducible p70 S6 kinase (p70s6k), a kinase which is essential for G1 progression. p70s6k mRNA and protein levels are enhanced 3-4-fold in various E1A-expressing cell lines. Similarly, the activity of p70s6k is enhanced in E1A-expressing cells in a manner partially independent of enhanced expression of p70s6k. The induction of p70s6k correlates with the presence of conserved region 1 (CR1) of E1A and with morphological transformation by E1A. These results suggest that induction of p70s6k by E1A might be involved in transformation by E1A.
Insights
Adenovirus E1A proteins enhance the expression and activity of p70 S6 kinase (p70s6k), a key regulator of cell cycle progression. This induction, linked to E1A
Area of Science:
- Molecular Biology
- Cell Biology
- Virology
Background:
- Adenovirus E1A proteins are known to induce cell transformation, often in cooperation with other oncogenes.
- The mechanism involves the modulation of critical cell cycle regulators.
- p70 S6 kinase (p70s6k) is a crucial kinase for cell cycle progression, particularly during the G1 phase.
Purpose of the Study:
- To investigate the effect of Adenovirus E1A on p70 S6 kinase (p70s6k) expression and activity.
- To determine the role of E1A-mediated p70s6k modulation in cellular transformation.
Main Methods:
- Quantification of p70s6k mRNA and protein levels in E1A-expressing cell lines.
- Assay of p70s6k kinase activity in cells expressing E1A.
- Correlation analysis between E1A conserved region 1 (CR1) and morphological transformation.
Main Results:
- Adenovirus E1A significantly enhances p70s6k mRNA and protein levels (3-4 fold) in various cell lines.
- p70s6k kinase activity is also elevated in E1A-expressing cells, partly independent of expression level changes.
- E1A-induced p70s6k expression correlates with the presence of conserved region 1 (CR1) and morphological transformation.
Conclusions:
- Adenovirus E1A protein upregulates both the expression and activity of p70 S6 kinase (p70s6k).
- The induction of p70s6k by E1A, particularly mediated by CR1, is suggested to contribute to cellular transformation.
- p70s6k is identified as a potential mediator in the E1A-driven oncogenic process.