Abstract
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 language | English |
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Pages (from-to) | 542-55 |
Number of pages | 14 |
Journal | Trends In Cell Biology |
Volume | 20 |
Issue number | 9 |
DOIs | |
Publication status | Published - Sept 2010 |
Keywords / Materials (for Non-textual outputs)
- Drug Discovery
- Humans
- Mutation
- Neoplasms
- Proto-Oncogene Proteins c-mdm2
- Signal Transduction
- Tumor Suppressor Protein p53