Abstract：
:Mathematical modeling is a powerful tool for unraveling the complexities of the molecular regulatory networks underlying all aspects of cell physiology. To support this claim, we review our experiences modeling the cyclin-dependent kinase (CDK) network that controls events of the eukaryotic cell cycle. The model was derived from classic experiments on the biochemistry and molecular genetics of CDKs and their partner proteins. Because the dynamical properties of CDK activity depend in large part on positive and negative feedback loops in the regulatory network, it is difficult to predict its behavior by intuitive reasoning alone. Mathematical modeling is the correct tool for reliably determining the properties of the network in comparison with observed properties of dividing cells and for predicting the behavior of the control system under novel conditions. In this review, we describe six unexpected predictions of our 1993 model of the CDK control system in frog egg extracts and the remarkable experiments, performed much later, that verified all six predictions. The dynamical properties of the CDK network are consequences of feedback signals and ultrasensitive responses of regulatory proteins to CDK activity, and we describe the experimental evidence for the predicted ultrasensitivity. This case study illustrates the novel insights that mathematical modeling, analysis, and simulation can provide cell physiologists, and it points the way to a new "dynamical perspective" on molecular cell biology.
journal_name
Bull Math Bioljournal_title
Bulletin of mathematical biologyauthors
Tyson JJ,Novak Bdoi
10.1007/s11538-014-0009-9subject
Has Abstractpub_date
2015-05-01 00:00:00pages
796-816issue
5eissn
0092-8240issn
1522-9602journal_volume
77pub_type
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