Regulated Degradation is a Mechanism for Suppressing
Stochastic Fluctuations in Gene Regulatory Networks
Hana El-Samad 1 and Mustafa Khammash 1*
1 University of California, Santa Barbara
* To whom correspondence should be addressed. E-mail: khammash{at}engineering.ucsb.edu.
Submitted on February 1, 2005
Revised on April 15, 2005
Accepted on 8 December 2005
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Abstract |
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Cellular events that execute life programs are ordered and reproducible despite the noise and randomness underlying their biochemical reactions. The identification of the processes that ensure this robust operation is essential not only to uncover the salient design principles in organisms, but also to forward engineer reliable genetic networks for biotechnological and therapeutic purposes. The use of feedback for noise reduction has been suggested as a recurring motif in genetic networks. In this work, we show how regulated degradation of proteins implements a negative feedback loop that enhances robustness against stochastic fluctuations and cellular noise. The analysis is carried out in the context of the bacterial heat shock response where the tight control of the amount of heat shock proteins (hsps) is achieved through an intricate architecture of feedback loops involving the sigma-32 factor. Sigma-32 regulates the transcription of hsps under normal and stress conditions. An essential feature of the heat shock response is a feedback loop regulating the degradation of sigma-32. We investigate the noise rejection properties of this loop to illustrate our point in a biologically plausible example.
Key Words:
biochemical noise, gene regulatory network, heat shock response, noise attenuation, regulated degradation, stochastic simulation
