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Dissecting the calcium-induced differentiation of human primary keratinocytes stem cells by integrative and structural network analyses

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dc.contributor.author Toufighi, Kiana, 1980-
dc.contributor.author Yang, Jae-Seong
dc.contributor.author Luis, Nuno Miguel, 1982-
dc.contributor.author Aznar Benitah, Salvador
dc.contributor.author Lehner, Ben, 1978-
dc.contributor.author Serrano Pubull, Luis, 1982-
dc.contributor.author Kiel, Christina
dc.date.accessioned 2015-11-18T19:26:57Z
dc.date.available 2015-11-18T19:26:57Z
dc.date.issued 2015
dc.identifier.citation Toufighi K, Yang JS, Luis NM, Aznar Benitah S, Lehner B, Serrano L et al. Dissecting the calcium-induced differentiation of human primary keratinocytes stem cells by integrative and structural network analyses. PLoS computational biology. 2015;11(5):e1004256. DOI: 10.1371/journal.pcbi.1004256
dc.identifier.issn 1553-734X
dc.identifier.uri http://hdl.handle.net/10230/25145
dc.description.abstract The molecular details underlying the time-dependent assembly of protein complexes in cellular networks, such as those that occur during differentiation, are largely unexplored. Focusing on the calcium-induced differentiation of primary human keratinocytes as a model system for a major cellular reorganization process, we look at the expression of genes whose products are involved in manually-annotated protein complexes. Clustering analyses revealed only moderate co-expression of functionally related proteins during differentiation. However, when we looked at protein complexes, we found that the majority (55%) are composed of non-dynamic and dynamic gene products ('di-chromatic'), 19% are non-dynamic, and 26% only dynamic. Considering three-dimensional protein structures to predict steric interactions, we found that proteins encoded by dynamic genes frequently interact with a common non-dynamic protein in a mutually exclusive fashion. This suggests that during differentiation, complex assemblies may also change through variation in the abundance of proteins that compete for binding to common proteins as found in some cases for paralogous proteins. Considering the example of the TNF-α/NFκB signaling complex, we suggest that the same core complex can guide signals into diverse context-specific outputs by addition of time specific expressed subunits, while keeping other cellular functions constant. Thus, our analysis provides evidence that complex assembly with stable core components and competition could contribute to cell differentiation.
dc.description.sponsorship KT is funded by a La Caixa PhD fellowship. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement Nr. PRIMES_278568 (to LS). This work was supported by the Spanish Ministerio de Economía y Competitividad, Plan Nacional BIO2012- 39754 and the European Fund for Regional Development.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Public Library of Science (PLoS)
dc.relation.ispartof PLoS computational biology. 2015;11(5):e1004256
dc.rights © 2015 Toufighi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.other Calci
dc.subject.other Proteïnes
dc.subject.other Genètica
dc.title Dissecting the calcium-induced differentiation of human primary keratinocytes stem cells by integrative and structural network analyses
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1371/journal.pcbi.1004256
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/278568
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BIO2012-39754
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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