Abrogation of p53-mediated transactivation by SV40 large T antigen.
p53 is known to bind specifically to the 44-bp human DNA sequence in an immunoprecipitation assay. We show here that the transcription of the reporter CAT gene linked with the herpesvirus thymidine kinase (tk) promoter containing the 44-base sequence is enhanced by mouse wild-type but not mutant-type p53 in F9 and p53-null Saos-2 cells. The p53-mediated transactivation was dramatically abrogated by introduction of SV40 large T antigen (SVLT) in Saos-2 cells in which p53 was clearly associated with SVLT. Furthermore, the p53-SVLT complex did not bind to the 44-base sequence at all. Thus, SVLT sequesters the transactivation function of the wild-type p53 by inhibiting the binding of p53 to the 44-base sequence. This is good evidence to show 'loss of functions' in the product of a tumor-suppressor oncogene by a dominant oncogene product at a molecular level.
Department of Microbiology, School of Medicine, Keio University, Tokyo, Japan.
K
K
Segawa
A
A
Minowa
K
K
Sugasawa
T
T
Takano
F
F
Hanaoka
D000952:Antigens, Polyomavirus Transforming / Q000494:pharmacology*; D001483:Base Sequence; D004261:DNA Replication; D016158:Genes, p53; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000378:metabolism; D013539:Simian virus 40 / Q000276:immunology*; D015533:Transcriptional Activation / Q000187:drug effects*
D000952:Antigens, Polyomavirus Transforming; D009841:Oligonucleotides