Browsing by Keyword "Ras"
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Publication Context-Dependent Impact of RAS Oncogene Expression on Cellular Reprogramming to Pluripotency(Elsevier, 2019-05-14) Ferreirós, Alba; Pedrosa, Pablo; Da Silva-Álvarez, Sabela; Triana-Martínez, Francisco; Vilas, Jéssica M; Picallos-Rabina, Pilar; Gonzalez, Patricia; Gomez Gil, Maria; Li, Han; García-Caballero, Tomás; González-Barcia, Miguel; Vidal, Anxo; Collado, Manuel; Ministerio de Ciencia e Innovación (España); Xunta de Galicia (España)Induction of pluripotency in somatic cells with defined genetic factors has been successfully used to investigate the mechanisms of disease initiation and progression. Cellular reprogramming and oncogenic transformation share common features; both involve undergoing a dramatic change in cell identity, and immortalization is a key step for cancer progression that enhances reprogramming. However, there are very few examples of complete successful reprogramming of tumor cells. Here we address the effect of expressing an active oncogene, RAS, on the process of reprogramming and found that, while combined expression with reprogramming factors enhanced dedifferentiation, expression within the context of neoplastic transformation impaired reprogramming. RAS induces expression changes that promote loss of cell identity and acquisition of stemness in a paracrine manner and these changes result in reprogramming when combined with reprogramming factors. When cells carry cooperating oncogenic defects, RAS drives cells into an incompatible cellular fate of malignancy.Publication Exploring the interactions of the RAS family in the human protein network and their potential implications in RAS-directed therapies.(2016) Bueno, Anibal; Morilla, Ian; Diez, Diego; Moya-Garcia, Aurelio A; Lozano, José; Ranea, Juan A G; [Bueno, Anibal] Univ Malaga, Dept Biol Mol & Bioquim, Malaga, Spain; [Lozano, Jose] Univ Malaga, Dept Biol Mol & Bioquim, Malaga, Spain; [Ranea, Juan A. G.] Univ Malaga, Dept Biol Mol & Bioquim, Malaga, Spain; [Morilla, Ian] Univ Zurich, Inst Mol Life Sci, Zurich, Switzerland; [Diez, Diego] Osaka Univ, World Premier Int Immunol Frontier Res Ctr, Quantitat Immunol Res Unit, Suita, Osaka , Japan; [Moya-Garcia, Aurelio A.] UCL, Inst Struct & Mol Biol, London, England; [Lozano, Jose] Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, Malaga, Spain; [Ranea, Juan A. G.] Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, Malaga , Spain; [Ranea, Juan A. G.] CIBER Enfermedades Raras, Madrid, SpainRAS 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.Publication Mammalian son of sevenless Guanine nucleotide exchange factors: old concepts and new perspectives(Impact Journals, 2011-03) Rojas-Cabañeros, Jose Maria; Oliva-Martinez, Jose Luis; Santos, Eugenio; Instituto de Salud Carlos III; Red Temática de Investigación Cooperativa en Cáncer (RTICC) (España); Asociación Española Contra el Cáncer; Junta de Castilla y León (España)The Son of Sevenless (Sos) factors were originally discovered 2 decades ago as specialized Ras activators in signaling pathways controlling the process of R7 cell development in the eye of Drosophila melanogaster. The 2 known members of the mammalian Sos family (Sos1 and Sos2) code for ubiquitously expressed, highly homologous (69% overall) proteins involved in coupling signals originated by cell surface receptor tyrosine kinases (RTKs) to downstream, Ras-dependent mitogenic signaling pathways. Mechanistically, the Sos proteins function as enzymatic factors interacting with Ras proteins in response to upstream stimuli to promote guanine nucleotide exchange (GDP/GTP) and subsequent formation of the active Ras-GTP complex. In this review, we summarize current knowledge on structural, regulatory, and functional aspects of the Sos family, focusing on specific aspects of Sos biology such as structure-function relationship, crosstalk with different signaling pathways, and in vivo functional significance as deduced from phenotypic characterization of Sos knockout mice and human genetic syndromes caused by germline hSos1 mutations.