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Network Biology, 2011, 1(1): 59-71
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Article

The role of protein interaction domains in the human cancer network

Shady S. Ibrahim1, Maha AR. Eldeeb1, Mona AH. Rady1, Karim M. Abdel Hady1, Mohamed S. Lotfy1, Noha S. Farag1, Stephan Verleysdonk2 and Christoph P. Bagowski3
1German University Cairo, Faculty of Pharmacy and Biotechnology, New Cairo City, Egypt; 2Interfaculty Institute for Biochemistry, University of T¨¹bingen, Hoppe-Seyler-Str. 4, 72076 T¨¹bingen, Germany; 33Centogene GmbH, Department of New Technologies, 18057 Rostock, Germany

Received 18 March 2011; Accepted 21 April 2011; Published online 14 May 2011
IAEES

Abstract
Protein-protein interaction networks provide a global picture of cellular function and biological processes. Proteins interact largely through specific domains which constitute the main building blocks of an interaction network. Perturbed or dysfunctional protein interactions are linked to many diseases, including cancer. In this study we describe the major pathways and connections within the human cancer network by a novel approach in which we overlay the human cancer network with all protein interaction domain (PID) superfamilies. Based on 38,777 experimentally derived interactions, we constructed a cancer network with 8 different levels and identified all major protein hubs within this cancer interactome. Only one percent of the cancer genes constitute over 50 percent of all interactions within the network. In addition, we mapped 56 PID superfamilies onto the cancer network, and discovered that over 10% of protein interaction domains are overrepresented within the cancer interactome when compared to the normal protein network. We present here a comprehensive list of all PIDs in the cancer network, identify the most important hubs within it and discover several individual genes which had previously not been linked to cancer. These proteins constitute excellent targets for the development of novel cancer therapeutics. Our results further hint to a partial molecular commonality between cancer and neurodegenerative diseases such as Alzheimer's and Huntington's.

Keywords protein domain; interaction network; PDZ domain; systems biology; cancer; tumour; superfamily;metastasis; interactome; p53; signaling; protein binding; neurodegenerative disease; Alzheimer; Huntington;NMDAR.



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