Stimulus-dependent dynamics of p53 in single cells

Batchelor, E.; Loewer, A.; Mock, C.; Lahav, G.

Stimulus-dependent dynamics of p53 in single cells

Tools

PDF - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
1MB

Item Type:	Article
Title:	Stimulus-dependent dynamics of p53 in single cells
Creators Name:	Batchelor, E., Loewer, A., Mock, C. and Lahav, G.
Abstract:	Many biological networks respond to various inputs through a common signaling molecule that triggers distinct cellular outcomes. One potential mechanism for achieving specific input-output relationships is to trigger distinct dynamical patterns in response to different stimuli. Here we focused on the dynamics of p53, a tumor suppressor activated in response to cellular stress. We quantified the dynamics of p53 in individual cells in response to UV and observed a single pulse that increases in amplitude and duration in proportion to the UV dose. This graded response contrasts with the previously described series of fixed pulses in response to γ-radiation. We further found that while γ-triggered p53 pulses are excitable, the p53 response to UV is not excitable and depends on continuous signaling from the input-sensing kinases. Using mathematical modeling and experiments, we identified feedback loops that contribute to specific features of the stimulus-dependent dynamics of p53, including excitability and input-duration dependency. Our study shows that different stresses elicit different temporal profiles of p53, suggesting that modulation of p53 dynamics might be used to achieve specificity in this network.
Keywords:	DNA Damage, Dynamics, Excitability, Feedback, Live-Cell Imaging
Source:	Molecular Systems Biology
ISSN:	1744-4292
Publisher:	Nature Publishing Group
Volume:	7
Page Range:	488
Date:	10 May 2011
Official Publication:	https://doi.org/10.1038/msb.2011.20
PubMed:	View item in PubMed

Repository Staff Only: item control page

Download Statistics

Downloads

Downloads per month over past year