A human protein-protein interaction network: a resource for annotating the proteome.by: U Stelzl, U Worm, M Lalowski, C Haenig, FH Brembeck, H Goehler, M Stroedicke, M Zenkner, A Schoenherr, S Koeppen, J Timm, S Mintzlaff, C Abraham, N Bock, S Kietzmann, A Goedde, E Toksöz, A Droege, S Krobitsch, B Korn, W Birchmeier, H Lehrach, EE Wanker
Cell, Vol. 122, No. 6. (23 September 2005), pp. 957-968.
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AbstractProtein-protein interaction maps provide a valuable framework for a better understanding of the functional organization of the proteome. To detect interacting pairs of human proteins systematically, a protein matrix of 4456 baits and 5632 preys was screened by automated yeast two-hybrid (Y2H) interaction mating. We identified 3186 mostly novel interactions among 1705 proteins, resulting in a large, highly connected network. Independent pull-down and coimmunoprecipitation assays validated the overall quality of the Y2H interactions. Using topological and GO criteria, a scoring system was developed to define 911 high-confidence interactions among 401 proteins. Furthermore, the network was searched for interactions linking uncharacterized gene products and human disease proteins to regulatory cellular pathways. Two novel Axin-1 interactions were validated experimentally, characterizing ANP32A and CRMP1 as modulators of Wnt signaling. Systematic human protein interaction screens can lead to a more comprehensive understanding of protein function and cellular processes.
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