Cell-specific modulation of the papovavirus promoters by tumor-suppressor protein p53 in the absence of large T-antigen.
The oncoproteins from several DNA tumor viruses form a complex with p53 and inactivate its function. Wild-type p53 is a transcription factor and can regulate eukaryotic promoters both positively and negatively. To elucidate the basis of the opposing functions and to understand whether and how oncoprotein synthesis in papovaviruses is regulated by p53, we studied modulation of the early promoters of SV40, polyomavirus and BK virus in the absence of the interfering effect of viral large T antigens. We here show that murine p53 can regulate the viral promoters either positively or negatively depending on the cell type. A temperature-sensitive mutant p53, 135 Val, at 37 degrees C also showed a cell-specific effect. These results suggest that promoter activation by p53 is not solely determined by p53 binding site, but host factors modulate p53's transactivation function. A TATA-less polyomavirus late promoter was also repressed in HeLa cells and the level of repression was much less in the presence of active early promoter. As p53 and 135 Val were overexpressed to similar extent in different transfected cell lines, variation in transactivation function is not due to the difference in the level of expressed protein. Our observations thus suggest that p53 interactions with cellular factors in addition to the TATA binding protein (TBP) are important for activator and repressor functions of p53. Well-defined viral promoters could thus provide us with an important tool for the identification and characterization of cellular factors that modulate p53-binding dependent gene regulation in animal cells.
Department of Molecular Biology, University of Texas Health Science Center at Tyler, 75710.
G C
GC
Das
C V
CV
Shivakumar
S D
SD
Todd
D016475:3T3 Cells; D000818:Animals; D001739:BK Virus / Q000235:genetics; D002460:Cell Line; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D027383:Papillomaviridae / Q000235:genetics*; D027382:Polyomaviridae; D011120:Polyomavirus / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013539:Simian virus 40 / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000502:physiology*
D016159:Tumor Suppressor Protein p53