Drug discovery and mutant p53

Magda M Maslon, Ted R Hupp

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Missense mutations in the p53 gene are commonly selected for in developing human cancer cells. These diverse mutations in p53 can inactivate its normal sequence-specific DNA-binding and transactivation function, but these mutations can also stabilize a mutant form of p53 with pro-oncogenic potential. Recent multi-disciplinary advances have demonstrated exciting and unexpected potential in therapeutically targeting the mutant p53 pathway, including: the development of biophysical models to explain how mutations inactivate p53 and strategies for refolding and reactivation of mutant p53, the ability of mutant p53 protein to escape MDM2-mediated degradation in human cancers, and the growing 'interactome' of mutant p53 that begins to explain how the mutant p53 protein can contribute to diverse oncogenic and pro-metastatic signaling. Our rapidly accumulating knowledge on mutant p53-signaling pathways will facilitate drug discovery programmes in the challenging area of protein-protein interactions and mutant protein conformational control.
Original languageEnglish
Pages (from-to)542-55
Number of pages14
JournalTrends In Cell Biology
Volume20
Issue number9
DOIs
Publication statusPublished - Sept 2010

Keywords / Materials (for Non-textual outputs)

  • Drug Discovery
  • Humans
  • Mutation
  • Neoplasms
  • Proto-Oncogene Proteins c-mdm2
  • Signal Transduction
  • Tumor Suppressor Protein p53

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