Activating mutations in p53 produce a common conformational effect. A monoclonal antibody specific for the mutant form.

摘要: Point mutations in the p53 gene are most frequently identified genetic change human cancer. They convert murine from a tumour suppressor into dominant transforming oncogene able to immortalize primary cells and bring about full transformation combination with an activated ras gene. In both systems lie regions of conserved man Xenopus. We have developed monoclonal antibody designated PAb240 which does not immunoprecipitate wild type p53. A series different mutants all react more strongly than PAb246. The reactive form cannot bind SV40 large T antigen but HSP70. contrast, PAb246 binds recognizes forms when they denatured. It reacts mammalian chicken immunoblots. propose that immunoprecipitation by is diagnostic mutation suggest point recessive exert common conformational effect on protein. This abolishes binding promotes self-oligomerization. These results consistent negative model where mutant protein neutralizes activity conformation.