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dc.contributor.authorFrenkel-Morgenstern, Milana
dc.contributor.authorGorohovski, Alessandro
dc.contributor.authorTagore, Somnath
dc.contributor.authorSekar, Vaishnovi
dc.contributor.authorVazquez, Miguel
dc.contributor.authorValencia, Alfonso
dc.identifier.citationNucleic Acids Res. 2017 ;45(12):7094-7105.es_ES
dc.description.abstractFusion proteins, comprising peptides deriving from the translation of two parental genes, are produced in cancer by chromosomal aberrations. The expressed fusion protein incorporates domains of both parental proteins. Using a methodology that treats discrete protein domains as binding sites for specific domains of interacting proteins, we have cataloged the protein interaction networks for 11 528 cancer fusions (ChiTaRS-3.1). Here, we present our novel method, chimeric protein-protein interactions (ChiPPI) that uses the domain-domain co-occurrence scores in order to identify preserved interactors of chimeric proteins. Mapping the influence of fusion proteins on cell metabolism and pathways reveals that ChiPPI networks often lose tumor suppressor proteins and gain oncoproteins. Furthermore, fusions often induce novel connections between non-interactors skewing interaction networks and signaling pathways. We compared fusion protein PPI networks in leukemia/lymphoma, sarcoma and solid tumors finding distinct enrichment patterns for each disease type. While certain pathways are enriched in all three diseases (Wnt, Notch and TGF β), there are distinct patterns for leukemia (EGFR signaling, DNA replication and CCKR signaling), for sarcoma (p53 pathway and CCKR signaling) and solid tumors (FGFR and EGFR signaling). Thus, the ChiPPI method represents a comprehensive tool for studying the anomaly of skewed cellular networks produced by fusion proteins in cancer.es_ES
dc.description.sponsorshipThis work is funded by the Project Retos BFU2015- 71241-R of the Spanish Ministry of Economy, Industry and Competitiveness (MEIC), co-funded by European Re-gional Development Fund (ERDF) and by the ProjectPT13/0001/0030, Instituto de Salud Carlos III (ISCIII),Strategic Action in Health, co-funded by European Re-gional Development Fund (ERDF). The work of MFM issupported by the Israel Cancer Association (ICA) fund, the work of ST is supported by the VaTaT Postdoctoral Fel-lowship for excellent students [22351, 20027, 26912]. AV issupported by the Joint BSC-CRG-IRB Programme in Com- Downloaded from by Spanish National Cancer Research Center user on 04 February 2019 putational Biology. Funding for open access charge: ICA[e-cancer-diagnosis].Conflict of interest statement.None declared.es_ES
dc.publisherOxford University Presses_ES
dc.relation.isversionofPublisher's versiones_ES
dc.subject.meshHumans es_ES
dc.subject.meshMetabolic Networks and Pathways es_ES
dc.subject.meshOncogene Proteins, Fusion es_ES
dc.subject.meshPrecursor Cell Lymphoblastic Leukemia-Lymphoma es_ES
dc.subject.meshProtein Interaction Domains and Motifs es_ES
dc.subject.meshProtein Interaction Mapping es_ES
dc.subject.meshProtein Interaction Maps es_ES
dc.subject.meshReceptors, Notches_ES
dc.subject.meshSarcoma es_ES
dc.subject.meshSignal Transduction es_ES
dc.subject.meshTransforming Growth Factor beta es_ES
dc.subject.meshWnt Proteins es_ES
dc.subject.meshGene Expression Regulation, Neoplastic es_ES
dc.subject.meshSoftware es_ES
dc.titleChiPPI: a novel method for mapping chimeric protein-protein interactions uncovers selection principles of protein fusion events in canceres_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderMinisterio de Ciencia e Innovación (España)es_ES
dc.identifier.journalNucleic acids researches_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Biología Computacional Estructurales_ES

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