Thomas M, Kalita A, Labrecque S, Pim D, Banks L, Matlashewski G
International Centre for Genetic Engineering and Biotechnology, I-34012 Trieste, Italy.
Mol Cell Biol. 1999 Feb;19(2):1092-100. doi: 10.1128/MCB.19.2.1092.
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.
野生型p53蛋白在氨基酸72位存在一种常见的多态性，导致该位置出现脯氨酸残基（p53Pro）或精氨酸残基（p53Arg）。尽管这种变化导致蛋白质一级结构不同，进而在十二烷基硫酸钠-聚丙烯酰胺凝胶电泳中迁移率不同，但尚未报道这些野生型p53变体在生化或生物学特性上存在差异。我们最近发现，p53Arg比p53Pro对人乳头瘤病毒（HPV）E6蛋白诱导的降解更敏感。此外，这可能导致纯合p53Arg个体对HPV诱导的肿瘤易感性增加。在进一步研究这些p53变体的特性时，我们现在发现这两种形式在形态上都是野生型，并且在以序列特异性方式结合DNA的能力上没有差异。然而，p53变体在结合转录机制成分、激活转录、诱导凋亡以及抑制原代细胞转化的能力方面存在许多差异。这些观察结果可能对携带野生型p53序列的癌症的发生发展以及此类肿瘤对治疗的反应能力具有影响，具体取决于它们的p53基因型。
