The Transcription Factor E2F-1 in SV40 T Antigen-Induced Cerebellar Purkinje Cell Degeneration

Transgenic targeting of SV40 large T antigen (Tag) expression to murine cerebellar Purkinje cells induces these normally postmitotic neurons to undergo DNA synthesis and apoptosis. It has been proposed that these effects of Tag are due to the binding of Tag to pRb, which leads to the release and act...

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Bibliographic Details
Published in:Molecular and cellular neuroscience 1998-09, Vol.12 (1-2), p.16-28
Main Authors: Athanasiou, Maria C., Yunis, Wael, Coleman, Natalie, Ehlenfeldt, Robert, Clark, H.Brent, Orr, Harry T., Feddersen, Rodney M.
Format: Article
Language:English
Subjects:
Animals
Antigens, Polyomavirus Transforming - genetics
Antigens, Polyomavirus Transforming - metabolism
Blotting, Northern
Carrier Proteins
CDC2 Protein Kinase - genetics
Cell Adhesion Molecules, Neuronal
Cell Cycle Proteins
Contactin 2
DNA-Binding Proteins - analysis
DNA-Binding Proteins - physiology
E2F Transcription Factors
E2F1 Transcription Factor
Gene Expression - physiology
Membrane Glycoproteins - genetics
Mice
Mice, Transgenic
Nerve Degeneration - metabolism
Purkinje Cells - chemistry
Purkinje Cells - physiology
Retinoblastoma-Binding Protein 1
RNA, Messenger - metabolism
Simian virus 40
Transcription Factor DP1
Transcription Factors - analysis
Transcription Factors - physiology
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Summary:Transgenic targeting of SV40 large T antigen (Tag) expression to murine cerebellar Purkinje cells induces these normally postmitotic neurons to undergo DNA synthesis and apoptosis. It has been proposed that these effects of Tag are due to the binding of Tag to pRb, which leads to the release and activation of the transcription factor E2F. Here it is reported that E2F and CDC2, the protein product of a gene regulated by E2F, were detectable in the Purkinje cell nuclei of Tag expressing transgenic animals. To directly test whether E2F-1 is part of the mechanism of Tag-induced Purkinje cell degeneration, transgenic mice that overexpress E2F-1 specifically in cerebellar Purkinje cells were generated. Although E2F-1 itself did not affect Purkinje cells, it did accelerate Tag-induced ataxia and Purkinje cell loss, suggesting that E2F-1 can contribute to the mechanism of Tag-induced Purkinje cell degeneration.
ISSN:1044-7431
1095-9327
DOI:10.1006/mcne.1998.0699