2026-06-14T03:46:25Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/171152024-09-21T21:43:49Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud author Bueno, Anibal author Morilla, Ian author Diez, Diego author Moya-Garcia, Aurelio A author Lozano, José author Ranea, Juan A G authoraffiliation [Bueno, Anibal] Univ Malaga, Dept Biol Mol & Bioquim, Malaga, Spain authoraffiliation [Lozano, Jose] Univ Malaga, Dept Biol Mol & Bioquim, Malaga, Spain authoraffiliation [Ranea, Juan A. G.] Univ Malaga, Dept Biol Mol & Bioquim, Malaga, Spain authoraffiliation [Morilla, Ian] Univ Zurich, Inst Mol Life Sci, Zurich, Switzerland authoraffiliation [Diez, Diego] Osaka Univ, World Premier Int Immunol Frontier Res Ctr, Quantitat Immunol Res Unit, Suita, Osaka , Japan authoraffiliation [Moya-Garcia, Aurelio A.] UCL, Inst Struct & Mol Biol, London, England authoraffiliation [Lozano, Jose] Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, Malaga, Spain authoraffiliation [Ranea, Juan A. G.] Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, Malaga , Spain authoraffiliation [Ranea, Juan A. G.] CIBER Enfermedades Raras, Madrid, Spain 2024-01-16T12:15:49Z 2024-01-16T12:15:49Z 2016 10.18632/oncotarget.12416 1949-2553 Oncotarget http://hdl.handle.net/10668/10512 27713118 http://hdl.handle.net/20.500.12105/17115 RAS proteins are the founding members of the RAS superfamily of GTPases. They are involved in key signaling pathways regulating essential cellular functions such as cell growth and differentiation. As a result, their deregulation by inactivating mutations often results in aberrant cell proliferation and cancer. With the exception of the relatively well-known KRAS, HRAS and NRAS proteins, little is known about how the interactions of the other RAS human paralogs affect cancer evolution and response to treatment. In this study we performed a comprehensive analysis of the relationship between the phylogeny of RAS proteins and their location in the protein interaction network. This analysis was integrated with the structural analysis of conserved positions in available 3D structures of RAS complexes. Our results show that many RAS proteins with divergent sequences are found close together in the human interactome. We found specific conserved amino acid positions in this group that map to the binding sites of RAS with many of their signaling effectors, suggesting that these pairs could share interacting partners. These results underscore the potential relevance of cross-talking in the RAS signaling network, which should be taken into account when considering the inhibitory activity of drugs targeting specific RAS oncoproteins. This study broadens our understanding of the human RAS signaling network and stresses the importance of considering its potential cross-talk in future therapies. eng Ras cancer network signaling therapy Molecular interaction database Multiple sequence alignment K-ras Activation Inhibitors Inhibitors Inhibitors Discovery Target Cancer Genes Bind Exploring the interactions of the RAS family in the human protein network and their potential implications in RAS-directed therapies. research article