Disturbance rejection helps modulate the P53 oscillation

TitleDisturbance rejection helps modulate the P53 oscillation
Publication TypeJournal Article
Year of Publication2011
AuthorsShin, YJ, Lipkin, SM, Hencey, B, and Shen, X
JournalASME 2011 Dynamic Systems and Control Conference and Bath/ASME Symposium on Fluid Power and Motion Control, DSCC 2011
Volume2
Start Page557
Pagination557 - 563
Date Published12/2011
Abstract

Designing a system that adequately processes the input and that rejects the effects of disturbance is a central theme in feedback control theory. In this paper, we use the concept of "disturbance rejection" to analyze the oscillatory behavior of p53, a well-known tumor suppressor protein. Our analysis reveals that the p53 oscillation is not completely dictated by the p53-MDM2 negative feedback loopit is also modulated by periodic DNA repair-related fluctuations. According to our disturbance rejection model, the feedback loop normally filters the effects of noise and fluctuations on p53, but upon DNA damage, it stops performing the filtering function so that DNA repair-related fluctuations can modulate the p53 oscillation. Our analysis suggests that the overexpression of MDM2, observed in many types of cancer, can make the feedback mechanism less responsive to the modulating signals after DNA damage occurs. Copyright © 2011 by ASME.

DOI10.1115/DSCC2011-6046
Short TitleASME 2011 Dynamic Systems and Control Conference and Bath/ASME Symposium on Fluid Power and Motion Control, DSCC 2011