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 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.
Athanasiou
M C
MC
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, 55455, USA.
Yunis
W
W
Coleman
N
N
Ehlenfeldt
R
R
Clark
H B
HB
Orr
H T
HT
Feddersen
R M
RM
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics* / Q000378:metabolism; D015152:Blotting, Northern; D016203:CDC2 Protein Kinase / Q000235:genetics; D002352:Carrier Proteins; D015816:Cell Adhesion Molecules, Neuronal; D018797:Cell Cycle Proteins; D058969:Contactin 2; D004268:DNA-Binding Proteins / Q000032:analysis / Q000502:physiology; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D015870:Gene Expression / Q000502:physiology; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000378:metabolism*; D011689:Purkinje Cells / Q000737:chemistry / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000032:analysis / Q000502:physiology*
D000952:Antigens, Polyomavirus Transforming; C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D015816:Cell Adhesion Molecules, Neuronal; D018797:Cell Cycle Proteins; C548675:Cntn2 protein, mouse; D058969:Contactin 2; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D016203:CDC2 Protein Kinase