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Oscillations by the p53-Mdm2 Feedback Loop

Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 641)

Abstract

The p53 network is perhaps the most important pathway involved in preventing the initiation of cancer. p53 levels and activity are upregulated in response to various, stresses including DNA damage, hypoxia, and oncogene activation. Active p53 initiates different transcriptional programs that result in cell cycle arrest, cellular senescence or apoptosis. p53 also activates the transcription of Mdm2, which in turns target p53 for degradation, therefore creating a negative feedback loop on p53. Previous studies showed that the level of p53 increased dramatically after exposure to damaging radiation, then declined in a series of damped oscillations. Recent quantitative studies examined p53 responses in individual living cells, using time-lapse fluorescent microscopy and showed that—on an individual cell level—the oscillations are not damped. Instead one cell may have only one pulse of p53, while its neighbor may show several repeated pulses. As the amount of irradiation increased, the percentage of cells showing a high number of p53 pulses also increased. The mean height and width of the pulses was constant and did not depend on the damage level. These observations opened new questions regarding the mechanism and function of p53 oscillatory dynamics. In this chapter I will review the different models that have been suggested for p53 oscillations, including proposed reasons for variation between cells, and will discuss potential functions for oscillatory dynamics in the p53 signaling pathway and in stress responses in general.

Keywords

Feedback Loop Oscillatory Behavior Negative Feedback Loop Oscillatory Dynamic Undamped Oscillation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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© Landes Bioscience and Springer Science+Business Media 2008

Authors and Affiliations

  1. 1.Department of Systems BiologyHarvard Medical SchoolBostonUSA

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