The transcription factor E2F-1 in SV40 T antigen-induced cerebellar Purkinje cell degeneration

Maria C. Athanasiou, Wael Yunis, Natalie Coleman, Robert Ehlenfeldt, H. Brent Clark, Harry T. Orr, Rodney M. Feddersen

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)16-28
Number of pages13
JournalMolecular and Cellular Neurosciences
Volume12
Issue number1-2
DOIs
StatePublished - Sep 1998

Bibliographical note

Funding Information:
This work was supported by NIH Grants NS32320 (R.M.F.) and NS31318 (H.T.O., H.B.C., W.S.Y., and R.M.F.).

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