Gain of function of mutant p53 by coaggregation with multiple tumor suppressors.

  title={Gain of function of mutant p53 by coaggregation with multiple tumor suppressors.},
  author={Jie Xu and J. Reumers and Jos{\'e} R. Couceiro and Frederik De Smet and Rodrigo Gallardo and Stanislav G. Rudyak and Ann Cornelis and Jef Rozenski and Aleksandra K Zwolinska and Jean-Christophe Marine and Diether Lambrechts and Y Suh and Frederic Rousseau and Joost Schymkowitz},
  journal={Nature chemical biology},
  volume={7 5},
Many p53 missense mutations possess dominant-negative activity and oncogenic gain of function. We report that for structurally destabilized p53 mutants, these effects result from mutant-induced coaggregation of wild-type p53 and its paralogs p63 and p73, thereby also inducing a heat-shock response. Aggregation of mutant p53 resulted from self-assembly of a conserved aggregation-nucleating sequence within the hydrophobic core of the DNA-binding domain, which becomes exposed after mutation… CONTINUE READING
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