Activation of the cryptic DNA binding function of mutant forms of p53

T R Hupp, D W Meek, C A Midgley, D P Lane

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Wild type p53 assembles into a latent multiprotein complex which can be activated for sequence-specific DNA binding in vitro by proteins targeting the carboxy-terminal domain. Using an optimized system coupling the post-translational modification of wild type p53 to activation of sequence specific DNA binding, we examined the affects of common mutations on the cryptic DNA binding function of p53. Two mutant forms of p53 were shown to be efficiently converted from the latent state by PAb421 and DnaK, but were defective in activation by casein kinase II, indicating that mutant p53 may not be receptive to allosteric regulation by casein kinase II phosphorylation. A reactive sulfhydryl group is absolutely required for DNA binding by wild type and mutant forms of p53 once converted to the activated state. Together, these data show that some mutant forms of p53 harbour the wild-type machinery required to engage in sequence-specific DNA binding and define a signalling pathway whose inactivation may directly result in a loss of p53 function.
Original languageEnglish
Pages (from-to)3167-3174
Number of pages8
JournalNucleic Acids Research
Volume21
Issue number14
Publication statusPublished - 11 Jul 1993

Keywords / Materials (for Non-textual outputs)

  • Base Sequence
  • Casein Kinases
  • DNA
  • Gene Expression Regulation
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Phosphorylation
  • Protein Binding
  • Protein Kinases
  • Sulfhydryl Compounds
  • Tumor Suppressor Protein p53

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