TAILIEUCHUNG - Báo cáo khoa học: Topology, tinkering and evolution of the human transcription factor network

Patterns of protein interactions are organized around complex heterogene-ous networks. Their architecture has been suggested to be of relevance in understanding the interactome and its functional organization, which per-vades cellular robustness. Transcription factors are particularly relevant in this context, given their central role in gene regulation. | ềFEBS Journal Topology tinkering and evolution of the human transcription factor network Carlos Rodriguez-Caso1 2 Miguel A. Medina2 and Ricard V. Sole1 3 1 ICREA-Complex Systems Laboratory Universitat Pompeu Fabra Barcelona Spain 2 Department of Molecular Biology and Biochemistry Faculty of Sciences Universidad de Malaga Spain 3 Santa Fe Institute Santa Fe New Mexico USA Keywords human molecular evolution protein interaction tinkering transcription factor network Correspondence Ricard V. Sole ICREA- Complex System Laboratory Universitat Pompeu Fabra Dr Aiguader 80 08003 Barcelona Spain Fax 34 93 221 3237 Tel 34 93 542 2821 E-mail Received 5 August 2005 revised 25 October 2005 accepted 31 October 2005 doi Patterns of protein interactions are organized around complex heterogeneous networks. Their architecture has been suggested to be of relevance in understanding the interactome and its functional organization which pervades cellular robustness. Transcription factors are particularly relevant in this context given their central role in gene regulation. Here we present the first topological study of the human protein-protein interacting transcription factor network built using the TRANSFAC database. We show that the network exhibits scale-free and small-world properties with a hierarchical and modular structure which is built around a small number of key proteins. Most of these proteins are associated with proliferative diseases and are typically not linked to each other thus reducing the propagation of failures through compartmentalization. Network modularity is consistent with common structural and functional features and the features are generated by two distinct evolutionary strategies amplification and shuffling of interacting domains through tinkering and acquisition of specific interacting regions. The function of the regulatory complexes may have played an active role in choosing one of them. Living cells .

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