Kinetic mechanism of p53 oncogenic mutant aggregation and its inhibition.

@article{Wilcken2012KineticMO,
  title={Kinetic mechanism of p53 oncogenic mutant aggregation and its inhibition.},
  author={Rainer Wilcken and Guozhen Wang and Frank M. Boeckler and A. R. Fersht},
  journal={Proceedings of the National Academy of Sciences of the United States of America},
  year={2012},
  volume={109 34},
  pages={
          13584-9
        }
}
Aggregation of destabilized mutants of the tumor suppressor p53 is a major route for its loss of activity. In order to assay drugs that inhibit aggregation of p53, we established the basic kinetics of aggregation of its core domain, using the mutant Y220C that has a mutation-induced, druggable cavity. Aggregation monitored by light scattering followed lag kinetics. Electron microscopy revealed the formation of small aggregates that subsequently grew to larger amorphous aggregates. The kinetics… CONTINUE READING

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