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Post-translational regulation enables robust p53 regulation.

Publication ,  Journal Article
Shin, Y-J; Chen, K-Y; Sayed, AH; Hencey, B; Shen, X
Published in: BMC Syst Biol
August 30, 2013

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

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Published In

BMC Syst Biol

DOI

EISSN

1752-0509

Publication Date

August 30, 2013

Volume

7

Start / End Page

83

Location

England

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Systems Biology
  • Stochastic Processes
  • Reproducibility of Results
  • Proto-Oncogene Proteins c-mdm2
  • Protein Processing, Post-Translational
  • Nonlinear Dynamics
  • Models, Biological
  • Gene Expression Regulation
  • Feedback, Physiological
 

Citation

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Shin, Y.-J., Chen, K.-Y., Sayed, A. H., Hencey, B., & Shen, X. (2013). Post-translational regulation enables robust p53 regulation. BMC Syst Biol, 7, 83. https://doi.org/10.1186/1752-0509-7-83
Shin, Yong-Jun, Kai-Yuan Chen, Ali H. Sayed, Brandon Hencey, and Xiling Shen. “Post-translational regulation enables robust p53 regulation.BMC Syst Biol 7 (August 30, 2013): 83. https://doi.org/10.1186/1752-0509-7-83.
Shin Y-J, Chen K-Y, Sayed AH, Hencey B, Shen X. Post-translational regulation enables robust p53 regulation. BMC Syst Biol. 2013 Aug 30;7:83.
Shin, Yong-Jun, et al. “Post-translational regulation enables robust p53 regulation.BMC Syst Biol, vol. 7, Aug. 2013, p. 83. Pubmed, doi:10.1186/1752-0509-7-83.
Shin Y-J, Chen K-Y, Sayed AH, Hencey B, Shen X. Post-translational regulation enables robust p53 regulation. BMC Syst Biol. 2013 Aug 30;7:83.
Journal cover image

Published In

BMC Syst Biol

DOI

EISSN

1752-0509

Publication Date

August 30, 2013

Volume

7

Start / End Page

83

Location

England

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Systems Biology
  • Stochastic Processes
  • Reproducibility of Results
  • Proto-Oncogene Proteins c-mdm2
  • Protein Processing, Post-Translational
  • Nonlinear Dynamics
  • Models, Biological
  • Gene Expression Regulation
  • Feedback, Physiological