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Biophys J. Jun 2002; 82(6): 2943–2950.
PMCID: PMC1302082

Attenuation of noise in ultrasensitive signaling cascades.

Abstract

Ultrasensitive cascades often implement thresholding operations in cell signaling and gene regulatory networks, converting graded input signals into discrete all-or-none outputs. However, the biochemical and genetic reactions involved in such cascades are subject to random fluctuations, leading to noise in output signal levels. Here we prove that cascades operating near saturation have output signal fluctuations that are bounded in magnitude, even as the number of noisy cascade stages becomes large. We show that these fluctuation-bounded cascades can be used to attenuate the noise in an input signal, and we find the optimal cascade length required to achieve the best possible noise reduction. Cascades with ultrasensitive transfer functions naturally operate near saturation, and can be made to simultaneously implement thresholding and noise reduction. They are therefore ideally suited to mediate signal transfer in both natural and artificial biological networks.

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Selected References

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  • Becskei A, Serrano L. Engineering stability in gene networks by autoregulation. Nature. 2000 Jun 1;405(6786):590–593. [PubMed]
  • Berg OG, Paulsson J, Ehrenberg M. Fluctuations and quality of control in biological cells: zero-order ultrasensitivity reinvestigated. Biophys J. 2000 Sep;79(3):1228–1236. [PMC free article] [PubMed]
  • Chock PB, Stadtman ER. Superiority of interconvertible enzyme cascades in metabolite regulation: analysis of multicyclic systems. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2766–2770. [PMC free article] [PubMed]
  • Detwiler PB, Ramanathan S, Sengupta A, Shraiman BI. Engineering aspects of enzymatic signal transduction: photoreceptors in the retina. Biophys J. 2000 Dec;79(6):2801–2817. [PMC free article] [PubMed]
  • Ferrell JE., Jr Tripping the switch fantastic: how a protein kinase cascade can convert graded inputs into switch-like outputs. Trends Biochem Sci. 1996 Dec;21(12):460–466. [PubMed]
  • Ferrell JE, Jr, Machleder EM. The biochemical basis of an all-or-none cell fate switch in Xenopus oocytes. Science. 1998 May 8;280(5365):895–898. [PubMed]
  • Goldbeter A, Koshland DE., Jr An amplified sensitivity arising from covalent modification in biological systems. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6840–6844. [PMC free article] [PubMed]
  • Gustin MC, Albertyn J, Alexander M, Davenport K. MAP kinase pathways in the yeast Saccharomyces cerevisiae. Microbiol Mol Biol Rev. 1998 Dec;62(4):1264–1300. [PMC free article] [PubMed]
  • Hasty J, Pradines J, Dolnik M, Collins JJ. Noise-based switches and amplifiers for gene expression. Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2075–2080. [PMC free article] [PubMed]
  • Kalir S, McClure J, Pabbaraju K, Southward C, Ronen M, Leibler S, Surette MG, Alon U. Ordering genes in a flagella pathway by analysis of expression kinetics from living bacteria. Science. 2001 Jun 15;292(5524):2080–2083. [PubMed]
  • Kepler TB, Elston TC. Stochasticity in transcriptional regulation: origins, consequences, and mathematical representations. Biophys J. 2001 Dec;81(6):3116–3136. [PMC free article] [PubMed]
  • Lamb TD. Gain and kinetics of activation in the G-protein cascade of phototransduction. Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):566–570. [PMC free article] [PubMed]
  • McAdams HH, Arkin A. Stochastic mechanisms in gene expression. Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):814–819. [PMC free article] [PubMed]
  • McAdams HH, Arkin A. It's a noisy business! Genetic regulation at the nanomolar scale. Trends Genet. 1999 Feb;15(2):65–69. [PubMed]
  • Paulsson J, Berg OG, Ehrenberg M. Stochastic focusing: fluctuation-enhanced sensitivity of intracellular regulation. Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7148–7153. [PMC free article] [PubMed]
  • Stadtman ER, Chock PB. Superiority of interconvertible enzyme cascades in metabolic regulation: analysis of monocyclic systems. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2761–2765. [PMC free article] [PubMed]
  • Thattai M, van Oudenaarden A. Intrinsic noise in gene regulatory networks. Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8614–8619. [PMC free article] [PubMed]

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