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Boolean model of yeast apoptosis as a tool to study yeast and human apoptotic regulations

Laleh Kazemzadeh (Institutionen för kemi- och bioteknik) ; Marija Cvijovic (Institutionen för matematiska vetenskaper ; Institutionen för kemi- och bioteknik, Systembiologi) ; Dina Petranovic (Institutionen för kemi- och bioteknik, Systembiologi)
Frontiers in Physiology (1664-042X). Vol. 3 (2012),
[Artikel, refereegranskad vetenskaplig]

Programmed cell death (PCD) is an essential cellular mechanism that is evolutionary conserved, mediated through various pathways and acts by integrating different stimuli. Many diseases such as neurodegenerative diseases and cancers are found to be caused by, or associated with, regulations in the cell death pathways. Yeast Saccharomyces cerevisiae, is a unicellular eukaryotic organism that shares with human cells components and pathways of the PCD and is therefore used as a model organism. Boolean modeling is becoming promising approach to capture qualitative behavior and describe essential properties of such complex networks. Here we present large literature-based and to our knowledge first Boolean model that combines pathways leading to apoptosis (a type of PCD) in yeast. Analysis of the yeast model confirmed experimental findings of anti-apoptotic role of Bir1p and pro-apoptotic role of Stm1p and revealed activation of the stress protein kinase Hog proposing the maximal level of activation upon heat stress. In addition we extended the yeast model and created an in silico humanized yeast in which human pro- and anti-apoptotic regulators Bcl-2 family and Valosin-contain protein (VCP) are included in the model. We showed that accumulation of Bax in silico humanized yeast shows apoptotic markers and that VCP is essential target of Akt Signaling. The presented Boolean model provides comprehensive description of yeast apoptosis network behavior. Extended model of humanized yeast gives new insights of how complex human disease like neurodegeneration can initially be tested.

Nyckelord: apoptosis, Boolean modeling, Stm1, Bir1, Hog1,VCP, Bcl-2 family



Denna post skapades 2013-01-14. Senast ändrad 2016-12-05.
CPL Pubid: 170513

 

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Institutioner (Chalmers)

Institutionen för kemi- och bioteknik (2005-2014)
Institutionen för matematiska vetenskaperInstitutionen för matematiska vetenskaper (GU)
Institutionen för kemi- och bioteknik, Systembiologi (2008-2014)

Ämnesområden

Bioinformatik och systembiologi

Chalmers infrastruktur