RT Journal Article
T1 Exploring the interactions of the RAS family in the human protein network and their potential implications in RAS-directed therapies.
A1 Bueno, Anibal
A1 Morilla, Ian
A1 Diez, Diego
A1 Moya-Garcia, Aurelio A
A1 Lozano, José
A1 Ranea, Juan A G
K1 Ras
K1 cancer
K1 network
K1 signaling
K1 therapy
K1 Molecular interaction database
K1 Multiple sequence alignment
K1 K-ras
K1 Activation
K1 Inhibitors
K1 Inhibitors
K1 Inhibitors
K1 Discovery
K1 Target
K1 Cancer
K1 Genes
K1 Bind
AB 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.
YR 2016
FD 2016
LK http://hdl.handle.net/10668/10512
UL http://hdl.handle.net/10668/10512
LA en
DS RISalud
RD Apr 6, 2025