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          Institute: MPI für molekulare Genetik     Collection: Department of Vertebrate Genomics     Display Documents



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ID: 335112.0, MPI für molekulare Genetik / Department of Vertebrate Genomics
Proteomic shifts in embryonic stem cells with gene dose modifications suggest the presence of balancer proteins in protein regulatory networks
Authors:Mao, Lei; Zabel, Claus; Herrmann, Marion; Nolden, Tobias; Mertes, Florian; Magnol, Laetitia; Chabert, Caroline; Hartl, Daniela; Herault, Yann; Delabar, Jean Maurice; Manke, Thomas; Himmelbauer, Heinz; Klose, Joachim
Language:English
Date of Publication (YYYY-MM-DD):2007-11-28
Title of Journal:PLoS One
Volume:2
Issue / Number:11
Start Page:e1218
End Page:e1218
Copyright:Mao et al
Review Status:not specified
Audience:Experts Only
Abstract / Description: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.
Comment of the Author/Creator:E-mail: lei.mao@charite.de
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:Hans Lehrach
Affiliations:MPI für molekulare Genetik
External Affiliations:Institute for Human Genetics, Charité-University Medicine Berlin, Germany;
Institut de Transgénose, IEM, UMR6218, CNRS Uni Orléans, Orléans, France;
EA 3508, Université Paris Diderot-Paris 7, Paris, France
Identifiers:ISSN:1932-6203
DOI:10.1371/journal.pone.0001218
URL:http://www.pubmedcentral.nih.gov/picrender.fcgi?ar...
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