SV40 large T antigen with c-Jun down-regulates myelin P0 gene expression: a mechanism for papovaviral T antigen-mediated demyelination.
Expression of myelin proteins has been shown to be altered in transgenic mice that express papovaviral large tumor (T) antigens. This paper analyzes the effect on P0 gene expression in secondary Schwann cells transfected with the SV40 T antigen gene and in Schwann cells immortalized by T antigen. In secondary Schwann cells, both T antigen and c-Jun are required for significant inhibition of the P0 promoter; expression of only one of the proteins is insufficient for repression of the P0 gene. T antigen, c-Jun (p39), and c-Jun-related protein (p47) form an immunoprecipitable complex in SV40 immortalized Schwann cell lines, and T antigen and c-Jun bind independently and as a complex to the P0 promoter. Our data suggest that the probable molecular mechanism underlying the hypomyelination observed in transgenic animals expressing T antigen may be due to the repression of the P0 gene by T antigen and c-Jun.
Bharucha
V A
VA
Department of Pediatrics, University of Michigan, Ann Arbor 48109.
Peden
K W
KW
Tennekoon
G I
GI
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics* / Q000378:metabolism; D000956:Antigens, Viral / Q000276:immunology; D000957:Antigens, Viral, Tumor / Q000276:immunology; D001483:Base Sequence; D003711:Demyelinating Diseases / Q000276:immunology; D015536:Down-Regulation; D015870:Gene Expression; D008969:Molecular Sequence Data; D018993:Myelin P0 Protein; D009185:Myelin Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015345:Oligonucleotide Probes / Q000235:genetics; D027383:Papillomaviridae / Q000276:immunology; D027382:Polyomaviridae; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D012583:Schwann Cells / Q000378:metabolism; D014158:Transcription, Genetic
D000952:Antigens, Polyomavirus Transforming; D000956:Antigens, Viral; D000957:Antigens, Viral, Tumor; D018993:Myelin P0 Protein; D009185:Myelin Proteins; D015345:Oligonucleotide Probes; D016755:Proto-Oncogene Proteins c-jun