Analysis of a generic model of eukaryotic cell-cycle regulation

被引:187
作者
Csikasz-Nagy, Attila [1 ]
Battogtokh, Dorjsuren
Chen, Katherine C.
Novak, Bela
Tyson, John J.
机构
[1] Virginia Polytech Inst & State Univ, Dept Biol Sci, Blacksburg, VA 24061 USA
[2] Hungarian Acad Sci, Mol Network Dynam Res Grp, H-1521 Budapest, Hungary
[3] Budapest Univ Technol & Econ, Dept Agr & Chem Technol, H-1521 Budapest, Hungary
关键词
D O I
10.1529/biophysj.106.081240
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
We propose a protein interaction network for the regulation of DNA synthesis and mitosis that emphasizes the universality of the regulatory system among eukaryotic cells. The idiosyncrasies of cell cycle regulation in particular organisms can be attributed, we claim, to specific settings of rate constants in the dynamic network of chemical reactions. The values of these rate constants are determined ultimately by the genetic makeup of an organism. To support these claims, we convert the reaction mechanism into a set of governing kinetic equations and provide parameter values (specific to budding yeast, fission yeast, frog eggs, and mammalian cells) that account for many curious features of cell cycle regulation in these organisms. Using one-parameter bifurcation diagrams, we show how overall cell growth drives progression through the cell cycle, how cell-size homeostasis can be achieved by two different strategies, and how mutations remodel bifurcation diagrams and create unusual cell-division phenotypes. The relation between gene dosage and phenotype can be summarized compactly in two-parameter bifurcation diagrams. Our approach provides a theoretical framework in which to understand both the universality and particularity of cell cycle regulation, and to construct, in modular fashion, increasingly complex models of the networks controlling cell growth and division.
引用
收藏
页码:4361 / 4379
页数:19
相关论文
共 100 条
[91]   The JigCell Model Builder and Run Manager [J].
Vass, M ;
Allen, N ;
Shaffer, CA ;
Ramakrishnan, N ;
Watson, LT ;
Tyson, JJ .
BIOINFORMATICS, 2004, 20 (18) :3680-3681
[92]   The phosphatase Cdc14 triggers mitotic exit by reversal of CDK-dependent phosphorylation [J].
Visintin, R ;
Craig, K ;
Hwang, ES ;
Prinz, S ;
Tyers, M ;
Amon, A .
MOLECULAR CELL, 1998, 2 (06) :709-718
[93]   CDC20 and CDH1: A family of substrate-specific activators of APC-dependent proteolysis [J].
Visintin, R ;
Prinz, S ;
Amon, A .
SCIENCE, 1997, 278 (5337) :460-463
[94]   APC-dependent proteolysis of the mitotic cyclin Clb2 is essential for mitotic exit [J].
Wäsch, R ;
Cross, FR .
NATURE, 2002, 418 (6897) :556-562
[95]  
YANG LZ, IN PRESS J THEOR BIO
[96]   Control of cyclin ubiquitination by CDK-regulated binding of Hct1 to the anaphase promoting complex [J].
Zachariae, W ;
Schwab, M ;
Nasmyth, K ;
Seufert, W .
SCIENCE, 1998, 282 (5394) :1721-1724
[97]  
Zetterberg A., 1995, CELL CYCLE CONTROL, P206
[98]   Globally optimised parameters for a model of mitotic control in frog egg extracts [J].
Zwolak, JW ;
Tyson, JJ ;
Watson, LT .
IEE PROCEEDINGS SYSTEMS BIOLOGY, 2005, 152 (02) :81-92
[99]  
2006, GENERIC CELL CYCLE M
[100]  
2005, XPP XPPAUT