Document Detail

The transcription factor E2F-1 in SV40 T antigen-induced cerebellar Purkinje cell degeneration.
MedLine Citation:
PMID:  9770337     Owner:  NLM     Status:  MEDLINE    
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.
M C Athanasiou; W Yunis; N Coleman; R Ehlenfeldt; H B Clark; H T Orr; R M Feddersen
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular and cellular neurosciences     Volume:  12     ISSN:  1044-7431     ISO Abbreviation:  Mol. Cell. Neurosci.     Publication Date:  1998 Sep 
Date Detail:
Created Date:  1998-12-09     Completed Date:  1998-12-09     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9100095     Medline TA:  Mol Cell Neurosci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  16-28     Citation Subset:  IM    
Copyright Information:
Copyright 1998 Academic Press.
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, 55455, USA.
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MeSH Terms
Antigens, Polyomavirus Transforming / genetics*,  metabolism
Blotting, Northern
CDC2 Protein Kinase / genetics
Carrier Proteins*
Cell Adhesion Molecules, Neuronal*
Cell Cycle Proteins*
DNA-Binding Proteins / analysis,  physiology
E2F Transcription Factors
E2F1 Transcription Factor
Gene Expression / physiology
Membrane Glycoproteins / genetics
Mice, Transgenic
Nerve Degeneration / metabolism*
Purkinje Cells / chemistry,  physiology*
RNA, Messenger / metabolism
Retinoblastoma-Binding Protein 1
Transcription Factor DP1
Transcription Factors / analysis,  physiology*
Grant Support
Reg. No./Substance:
0/Antigens, Polyomavirus Transforming; 0/Arid4a protein, mouse; 0/Carrier Proteins; 0/Cell Adhesion Molecules, Neuronal; 0/Cell Cycle Proteins; 0/DNA-Binding Proteins; 0/E2F Transcription Factors; 0/E2F1 Transcription Factor; 0/E2f1 protein, mouse; 0/Membrane Glycoproteins; 0/RNA, Messenger; 0/Retinoblastoma-Binding Protein 1; 0/Transcription Factor DP1; 0/Transcription Factors; 0/contactin 2; EC Protein Kinase

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