Two polymorphic variants of wild-type p53 differ biochemically and biologically.
The wild-type p53 protein exhibits a common polymorphism at amino acid 72, resulting in either a proline residue (p53Pro) or an arginine residue (p53Arg) at this position. Despite the difference that this change makes in the primary structure of the protein resulting in a difference in migration during sodium dodecyl sulfate-polyacrylamide gel electrophoresis, no differences in the biochemical or biological characteristics of these wild-type p53 variants have been reported. We have recently shown that p53Arg is significantly more susceptible than p53Pro to the degradation induced by human papillomavirus (HPV) E6 protein. Moreover, this may result in an increased susceptibility to HPV-induced tumors in homozygous p53Arg individuals. In further investigating the characteristics of these p53 variants, we now show that both forms are morphologically wild type and do not differ in their ability to bind to DNA in a sequence-specific manner. However, there are a number of differences between the p53 variants in their abilities to bind components of the transcriptional machinery, to activate transcription, to induce apoptosis, and to repress the transformation of primary cells. These observations may have implications for the development of cancers which harbor wild-type p53 sequences and possibly for the ability of such tumors to respond to therapy, depending on their p53 genotype.
Thomas
M
M
International Centre for Genetic Engineering and Biotechnology, I-34012 Trieste, Italy.
Kalita
A
A
Labrecque
S
S
Pim
D
D
Banks
L
L
Matlashewski
G
G
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D004742:Enhancer Elements, Genetic; D016158:Genes, p53; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism; D027383:Papillomaviridae / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D051381:Rats; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology
D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D016159:Tumor Suppressor Protein p53; D004247:DNA