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Journal of Virology logoLink to Journal of Virology
. 1994 Apr;68(4):2206–2214. doi: 10.1128/jvi.68.4.2206-2214.1994

Modulation of cyclin gene expression by adenovirus E1A in a cell line with E1A-dependent conditional proliferation.

D Spitkovsky 1, P Steiner 1, J Lukas 1, E Lees 1, M Pagano 1, A Schulze 1, S Joswig 1, D Picard 1, M Tommasino 1, M Eilers 1, et al.
PMCID: PMC236696  PMID: 8139005

Abstract

To investigate how adenovirus E1A controls cell proliferation, we have fused E1A to the hormone-binding domain of the human estrogen receptor (ER) and introduced the E1A-ER chimeric gene together with an activated ras gene into primary rat embryo fibroblasts. Cell lines derived from this transfection proliferate in an estrogen-dependent manner. Estrogen-dependent activation of E1A-ER led to a rapid induction of both cyclin E and cyclin A gene expression. In contrast, levels of cyclin D1 were strongly reduced by activation of E1A-ER. Similar changes in cyclin gene expression were observed when primary human fibroblasts were infected with wild-type adenovirus and when adenovirus E1A was stably expressed in NIH 3T3 cells. Our findings suggest that activation of cyclin A and E, but not D1, gene expression by E1A precedes and may be responsible for E1A-dependent cell proliferation. In contrast, we found that quantitative disruption of complexes between the E2F transcription factor and the retinoblastoma protein is not required for E1A-dependent S-phase entry.

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Selected References

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