Journal
FEBS LETTERS
Volume 583, Issue 24, Pages 3992-3998Publisher
WILEY
DOI: 10.1016/j.febslet.2009.08.023
Keywords
Cell cycle; Bistability; Irreversibility; Feedback; Start; Mitotic exit
Funding
- Biotechnology and Biological Sciences Research Council Funding Source: Medline
- NIGMS NIH HHS [R01 GM079207-03, R01 GM078989-04, R01 GM078989, R01 GM079207] Funding Source: Medline
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Repetitive cell cycles, which are essential to the perpetuation of life, are orchestrated by an underlying biochemical reaction network centered around cyclin-dependent protein kinases (Cdks) and their regulatory subunits (cyclins). Oscillations of Cdk1/CycB activity between low and high levels during the cycle trigger DNA replication and mitosis in the correct order. Based on computational modeling, we proposed that the low and the high kinase activity states are alternative stable steady states of a bistable Cdk-control system. Bistability is a consequence of system-level feedback (positive and double-negative feedback signals) in the underlying control system. We have also argued that bistability underlies irreversible transitions between low and high Cdk activity states and thereby ensures directionality of cell cycle progression. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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