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Oscillations of Hes7 caused by negative autoregulation and ubiquitination

Paper ID Volume ID Publish Year Pages File Format Full-Text
15531 1421 2008 5 PDF Available
Title
Oscillations of Hes7 caused by negative autoregulation and ubiquitination
Abstract

Loss of Hes7 function leads to irregular somite formation demonstrating that Hes7 is a crucial component of the segmentation clock during somitogenesis. Experiments revealed that not only the repressor functionality but also the half-life of the protein is crucial for oscillatory expression of Hes7 and regular somite formation. Numerical integration of a delay equation system supported this finding. However, in a recent paper it was shown that the number of binding sites is also decisive for damped or undamped oscillations. It was shown that for more than one binding site the Hill coefficient increases. This leads to a completely different behavior. The oscillations are undamped and thus the mathematical model can no longer explain the results observed in the experiments.In this paper we propose a more sophisticated model for the Hes7 oscillator. Since Hes7 is degraded by the ubiquitin-proteasome pathway we include Michaelis-Menten kinetics for the ubiquitination of Hes7. We identify the Michaelis-Menten constant as an additional model parameter for oscillatory behavior. By increasing the Michaelis-Menten constant we found damped oscillations even if the Hill coefficient is increased.

Keywords
Hes7; Oscillation; Hill coefficient; Ubiquitination; Michaelis-Menten
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Oscillations of Hes7 caused by negative autoregulation and ubiquitination
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Publisher
Database: Elsevier - ScienceDirect
Journal: Computational Biology and Chemistry - Volume 32, Issue 1, February 2008, Pages 48–52
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
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Don't Miss Today's Special Offer
Price was $35.95
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Price after discount Only $4.95
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