P53 regulation

From Ilya Nemenman: Theoretical Biophysics @ Emory
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p53 is one of very important and very well studied regulatory systems, where effects of stochasticity have been noted. p53 responds to DNA damage in a digital matter, meaning that it pulses, and the number of pulses corresponds to the severity of the damage. Stochastic effects seem to be critical in determining reproducibility of the number of these oscillations. Interestingly, this system provides one of very few examples where a systems biology model is actually predictive in a common sense, allowing understanding of a phenomenon.


  1. L Ma, J Wagner, JJ Rice, W Hu, A Levine, and G Stolovitzky. A plausible model for the digital response of p53 to DNA damage. PNAS 102:14266, 2005. PDF, Supplementary.
  2. W Hu, Z Feng, L Ma, J Wagner, JJ Rice, G Stolovitzky, and A Levine. A Single Nucleotide Polymorphism in the MDM2 Gene Disrupts the Oscillation of p53 and MDM2 Levels in Cells. Cancer Res 67:2757, 2007. PDF.
  3. J Wagner, L Ma, JJ Rice, W Hu, A Levine, and G Stolovitzky. p53 – Mdm2 loop controlled by a balance of its feedback strength and effective dampening using ATM and delayed feedback. IEE Proc. Syst. Biol. 152:109, 2005. PDF.