Post-translational regulation enables robust p53 regulation.

Journal Article


The tumor suppressor protein p53 plays important roles in DNA damage repair, cell cycle arrest and apoptosis. Due to its critical functions, the level of p53 is tightly regulated by a negative feedback mechanism to increase its tolerance towards fluctuations and disturbances. Interestingly, the p53 level is controlled by post-translational regulation rather than transcriptional regulation in this feedback mechanism.


We analyzed the dynamics of this feedback to understand whether post-translational regulation provides any advantages over transcriptional regulation in regard to disturbance rejection. When a disturbance happens, even though negative feedback reduces the steady-state error, it can cause a system to become less stable and transiently overshoots, which may erroneously trigger downstream reactions. Therefore, the system needs to balance the trade-off between steady-state and transient errors. Feedback control and adaptive estimation theories revealed that post-translational regulation achieves a better trade-off than transcriptional regulation, contributing to a more steady level of p53 under the influence of noise and disturbances. Furthermore, post-translational regulation enables cells to respond more promptly to stress conditions with consistent amplitude. However, for better disturbance rejection, the p53- Mdm2 negative feedback has to pay a price of higher stochastic noise.


Our analyses suggest that the p53-Mdm2 feedback favors regulatory mechanisms that provide the optimal trade-offs for dynamic control.

Full Text

Duke Authors

Cited Authors

  • Shin, Y-J; Chen, K-Y; Sayed, AH; Hencey, B; Shen, X

Published Date

  • August 30, 2013

Published In

Volume / Issue

  • 7 /

Start / End Page

  • 83 -

PubMed ID

  • 23992617

Pubmed Central ID

  • 23992617

Electronic International Standard Serial Number (EISSN)

  • 1752-0509

International Standard Serial Number (ISSN)

  • 1752-0509

Digital Object Identifier (DOI)

  • 10.1186/1752-0509-7-83


  • eng