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Research Themes Protein-protein interactions

Click for cancer-protein interactions

PSI-SGKB [doi:10.1038/th_psisgkb.2008.20]
Technical Highlight - December 2008
Short description: The Human Cancer Pathway Protein Interaction Network (HCPIN) website makes structural information about cancer-related proteins easily accessible.Mol. Cell. Proteomics 7, 2048-2060 (2008)

A comprehensive analysis of the molecular basis of cancer requires information from many fields — biochemistry, genomics, cell biology, proteomics, structural biology and systems biology.

A complete understanding of the molecular interactions important in cancer biology cannot be achieved without high-resolution three-dimensional structures of cancer-related proteins. Without this information, key atomic details about binding interfaces and structural changes that accompany protein–protein interactions will be lacking.

Screenshot showing a representative protein interaction hub involving p53 from the Human Cancer Protein Interaction Network (HCPIN), a web-accessible database.

Although multiple databases exist to help make sense of the ever-growing data on protein–protein interactions and signaling pathways, a database that integrates this information with structural results has not been available until now.

Now, the PSI NESG has constructed a Human Cancer Pathway Protein Interaction Network (HCPIN) by analyzing several classic cancer-associated signaling pathways. The HCPIN website describes these biomedically important multipathway networks and provides experimental structures and homology models for HCPIN proteins.

Version 1 of the website includes more than 3,000 proteins and around 10,000 interactions, as well as 240 multiprotein complexes composed of at least three proteins. The seven pathways in the initial version are those involved in: cell-cycle progression; apoptosis; the MAP kinase cascade; the innate immunity response (including the Toll-like receptor); TGF-β; phosphatidylinositol-3-OH kinase; and JAK–STAT signaling. Well-known cancer proteins such as p53 and NFκB are also featured.

This version was constructed using information from the signaling pathway database KEGG together with protein–protein interaction data from the HPRD database. These were chosen because of the high quality of their curation. These data are combined with experimental structures from the Protein Data Bank and homology models based on protein structure templates that share over 80% sequence identity.

The long-range goal for the HCPIN is to provide a comprehensive three-dimensional structure–function database for human cancer-associated proteins. NESG is now targeting the proteins needed to complete the structural coverage of the HCPIN. The interaction map should provide information with which to generate multiprotein complexes for structural studies.

Future plans include mapping single nucleotide polymorphisms/mutation information and structural analysis of protein–protein interfaces, in addition to adding gene ontology and other structure-based functional annotations.

Maria Hodges

References

  1. Yuanpeng Janet Huang, Dehua Hang, Long Jason Lu, Liang Tong, Mark B. Gerstein and Gaetano T. Montelione. Targeting the Human Cancer Pathway Protein Interaction Network by structural genomics.
    Mol. Cell. Proteomics 7, 2048-2060 (2008). doi:10.1074/mcp.M700550-MCP200

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