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PLoS ONE 2, 11 (2007) e1218
Proteomic shifts in embryonic stem cells with gene dose modifications suggest the presence of balancer proteins in protein regulatory networks.
Lei Mao 1, Claus Zabel, Marion Herrmann 2, Tobias Nolden, Florian Mertes, Laetitia Magnol 3, Caroline Chabert, Daniela Hartl 4, Yann Herault 5, Jean Maurice Delabar 6, Thomas Manke, Heinz Himmelbauer 7, Joachim Klose 8
(2007)

Large numbers of protein expression changes are usually observed in mouse models for neurodegenerative diseases, even when only a single gene was mutated in each case. To study the effect of gene dose alterations on the cellular proteome, we carried out a proteomic investigation on murine embryonic stem cells that either overexpressed individual genes or displayed aneuploidy over a genomic region encompassing 14 genes. The number of variant proteins detected per cell line ranged between 70 and 110, and did not correlate with the number of modified genes. In cell lines with single gene mutations, up and down-regulated proteins were always in balance in comparison to parental cell lines regarding number as well as concentration of differentially expressed proteins. In contrast, dose alteration of 14 genes resulted in an unequal number of up and down-regulated proteins, though the balance was kept at the level of protein concentration. We propose that the observed protein changes might partially be explained by a proteomic network response. Hence, we hypothesize the existence of a class of "balancer" proteins within the proteomic network, defined as proteins that buffer or cushion a system, and thus oppose multiple system disturbances. Through database queries and resilience analysis of the protein interaction network, we found that potential balancer proteins are of high cellular abundance, possess a low number of direct interaction partners, and show great allelic variation. Moreover, balancer proteins contribute more heavily to the network entropy, and thus are of high importance in terms of system resilience. We propose that the "elasticity" of the proteomic regulatory network mediated by balancer proteins may compensate for changes that occur under diseased conditions.
1 :  Institute of Human Genetics
Charité Universitaets Berlin
2 :  Laboratoire d'aérologie (LA)
CNRS : UMR5560 – Observatoire Midi-Pyrénées – INSU – Université Paul Sabatier (UPS) - Toulouse III
3 :  Unité de Génétique Moléculaire Animale (UGMA)
Institut national de la recherche agronomique (INRA) : UMR1061 – Université de Limoges
4 :  Département d'O.R.L. et Chirurgie Cervico-Faciale
Institut Gustave Roussy
5 :  Immunologie et embryologie moléculaires (IEM)
CNRS : UMR6218 – Université d'Orléans
6 :  Biologie Fonctionnelle et Adaptative (BFA)
Université Paris VII - Paris Diderot : EA4413 – CNRS : EAC4413
7 :  Max-Planck-Institut für Molekulare Genetik
Max-Planck-Institut
8 :  Institute of Human Genetics
Charité Universitaets Berlin
Sciences du Vivant/Immunologie