کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2204840 | 1100828 | 2010 | 14 صفحه PDF | دانلود رایگان |
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.
Journal: - Volume 20, Issue 9, September 2010, Pages 542–555