In-silico modeling of the mitotic spindle assembly checkpoint

PloS One
Bashar IbrahimPeter Dittrich

Abstract

The Mitotic Spindle Assembly Checkpoint ((M)SAC) is an evolutionary conserved mechanism that ensures the correct segregation of chromosomes by restraining cell cycle progression from entering anaphase until all chromosomes have made proper bipolar attachments to the mitotic spindle. Its malfunction can lead to cancer. We have constructed and validated for the human (M)SAC mechanism an in silico dynamical model, integrating 11 proteins and complexes. The model incorporates the perspectives of three central control pathways, namely Mad1/Mad2 induced Cdc20 sequestering based on the Template Model, MCC formation, and APC inhibition. Originating from the biochemical reactions for the underlying molecular processes, non-linear ordinary differential equations for the concentrations of 11 proteins and complexes of the (M)SAC are derived. Most of the kinetic constants are taken from literature, the remaining four unknown parameters are derived by an evolutionary optimization procedure for an objective function describing the dynamics of the APC:Cdc20 complex. MCC:APC dissociation is described by two alternatives, namely the "Dissociation" and the "Convey" model variants. The attachment of the kinetochore to microtubuli is simulated by a...Continue Reading

References

May 16, 2014·PloS One·Michael C WeisSree N Sreenath
Sep 13, 2014·Nature Communications·Jing Chen, Jian Liu
Aug 5, 2009·PloS One·Andreas DoncicNaama Barkai
Aug 15, 2009·PLoS Computational Biology·Shenghua LiJohn J Tyson
Feb 2, 2013·PloS One·Dennis Görlich, Peter Dittrich
Apr 9, 2013·Progress in Biophysics and Molecular Biology·Sergej TschernyschkowBashar Ibrahim
Sep 19, 2009·Molecular BioSystems·Adrien Fauré, Denis Thieffry
Oct 23, 2014·International Journal of Molecular Sciences·Bashar Ibrahim, Richard Henze
Feb 28, 2015·Progress in Biophysics and Molecular Biology·Bashar Ibrahim
May 16, 2015·Computational and Structural Biotechnology Journal·Bashar Ibrahim
Apr 6, 2011·IEEE/ACM Transactions on Computational Biology and Bioinformatics·Jianyong SunCharlie Hodgman
Oct 17, 2012·PloS One·Peter KreyssigPeter Dittrich
Feb 7, 2008·PloS One·Bashar IbrahimPeter Dittrich
Jul 25, 2009·The EMBO Journal·Andrea Ciliberto, Jagesh V Shah
Nov 29, 2019·Cellular and Molecular Life Sciences : CMLS·Jan EwaldBashar Ibrahim
Nov 23, 2017·Mathematical Biosciences and Engineering : MBE·Bashar Ibrahim
Jun 22, 2017·Scientific Reports·Richard HenzeBashar Ibrahim

Citations

Nov 1, 1995·The Journal of Cell Biology·Kevin G Hardwick, A W Murray
Aug 1, 1995·The Journal of Cell Biology·R B NicklasGary J Gorbsky
Jan 31, 1997·Science·R B Nicklas
Jul 22, 1997·Proceedings of the National Academy of Sciences of the United States of America·X HeS Sazer
Mar 7, 1998·Science·L H HwangA W Murray
Aug 6, 1999·Molecular Biology of the Cell·R H ChenKevin G Hardwick
Mar 8, 2000·The Journal of Cell Biology·Kevin G HardwickA W Murray
Jul 20, 2001·Cell·H A Fisk, Mark Winey
Aug 28, 2002·The Journal of Cell Biology·Marko J KallioGary J Gorbsky
Oct 3, 2002·Nature Reviews. Molecular Cell Biology·Andrea Musacchio, Kevin G Hardwick
Oct 22, 2002·Molecular Biology of the Cell·Katie B ShannonE D Salmon
Nov 29, 2002·The EMBO Journal·Toshiyuki HabuTomohiro Matsumoto
Apr 11, 2003·Molecular Biology of the Cell·Song-Tao LiuTim J Yen
Jun 14, 2003·Evolutionary Computation·Nikolaus HansenPetros Koumoutsakos
Jul 12, 2003·Nature Cell Biology·Eunah Chung, Rey-Huei Chen
Oct 17, 2003·Genes & Development·Vincenzo D'AngiolellaDomenico Grieco
Feb 10, 2004·Nature Cell Biology·Michael A LampsonTarun M Kapoor
Feb 14, 2004·Cell Cycle·Harold A FiskMark Winey

Related Concepts

Cell Cycle Progression
Establishment and Maintenance of Localization
Biochemical Pathway
Spindle
Dynein Activity
BUB1B gene
CDC6 protein, human
Cell Cycle Proteins
Cdc20 Proteins
UBE2C gene

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.