Wild-type p53 activates transcription in vitro.
The p53 protein is an important determinant in human cancer and regulates the growth of cells in culture. It is known to be a sequence-specific DNA-binding protein with a powerful activation domain, but it has not been established whether it regulates transcription directly. Here we show that intact purified wild-type human and murine p53 proteins strongly activate transcription in vitro. This activation depends on the ability of p53 to bind to a template bearing a p53-binding sequence. By contrast, tumour-derived mutant p53 proteins cannot activate transcription from the template at all, and when complexed to wild-type p53, these mutants block transcriptional activation by the wild-type protein. Moreover, the simian virus 40 large T antigen inhibits wild-type p53 from activating transcription. Our results support a model in which p53 directly activates transcription but this activity can be inhibited by mutant p53 and SV40 large T antigen through interaction with wild-type p53.
Farmer
G
G
Department of Biological Sciences, Columbia University, New York 10027.
Bargonetti
J
J
Zhu
H
H
Friedman
P
P
Prywes
R
R
Prives
C
C
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000502:physiology*
D000952:Antigens, Polyomavirus Transforming; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53