Exploring the interactions of the RAS family in the human protein network and their potential implications in RAS-directed therapies

摘要: // Anibal Bueno 1 , Ian Morilla 2 Diego Diez 3 Aurelio A. Moya-Garcia 4 Jose Lozano 1, 5 Juan A.G. Ranea 5, 6 Departmento de Biologia Molecular y Bioquimica, Universidad Malaga, Malaga 29071, Spain Institute of Life Sciences, University Zurich, Zurich CH-8057, Switzerland Quantitative Immunology Research Unit, World Premier International Frontier Center, Osaka University, 565-0871, Japan Structural and Biology, College London, London WC1E 6BT, UK Instituto Investigacion Biomedica (IBIMA), Hospital Universitario Virgen la Victoria, 29010, CIBER Enfermedades Raras, Madrid 28029, Correspondence to: Ranea, email: ranea@uma.es Keywords: Ras, network, cancer, signaling, therapy Received: May 12, 2016      Accepted: September 15, Published: October 03, 2016 ABSTRACT RAS proteins are the founding members superfamily GTPases. They involved in key signaling pathways regulating essential cellular functions such as cell growth differentiation. As a result, their deregulation by inactivating mutations often results aberrant proliferation cancer. With exception relatively well-known KRAS, HRAS NRAS proteins, little is known about how interactions other human paralogs affect cancer evolution response to treatment. In this study we performed comprehensive analysis relationship between phylogeny location protein interaction network. This was integrated with structural conserved positions available 3D structures complexes. Our show that many divergent sequences found close together interactome. We specific amino acid group map binding sites effectors, suggesting these pairs could share interacting partners. These underscore potential relevance cross-talking which should be taken into account when considering inhibitory activity drugs targeting oncoproteins. broadens our understanding network stresses importance its cross-talk future therapies.