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dc.contributor.authorFerrer-Mayorga, Gemmaes_ES
dc.contributor.authorÁlvarez-Díaz, S.es_ES
dc.contributor.authorValle, Noeliaes_ES
dc.contributor.authorDe Las Rivas, Javieres_ES
dc.contributor.authorMendes, Martaes_ES
dc.contributor.authorBarderas, Rodrigoes_ES
dc.contributor.authorCasal, J. Ignacioes_ES
dc.contributor.authorLafarga, Migueles_ES
dc.contributor.authorMuñoz Terol, Albertoes_ES
dc.date.accessioned2016-02-26T09:36:44Z-
dc.date.available2016-02-26T09:36:44Z-
dc.date.issued2015-10-30-
dc.identifier.citationJournal of Biological Chemistry 290(44): 26533-26548 (2015)es_ES
dc.identifier.issn0021-9258-
dc.identifier.urihttp://hdl.handle.net/10261/129490-
dc.descriptionFerrer-Mayorga, Gemma et al.es_ES
dc.description.abstractCystatin D is an inhibitor of lysosomal and secreted cysteine proteases. Strikingly, cystatin D has been found to inhibit proliferation, migration, and invasion of colon carcinoma cells indicating tumor suppressor activity that is unrelated to protease inhibition. Here, we demonstrate that a proportion of cystatin D locates within the cell nucleus at specific transcriptionally active chromatin sites. Consistently, transcriptomic analysis show that cystatin D alters gene expression, including that of genes encoding transcription factors such as RUNX1, RUNX2, and MEF2C in HCT116 cells. In concordance with transcriptomic data, quantitative proteomic analysis identified 292 proteins differentially expressed in cystatin D-expressing cells involved in cell adhesion, cytoskeleton, and RNA synthesis and processing. Furthermore, using cytokine arrays we found that cystatin D reduces the secretion of several protumor cytokines such as fibroblast growth factor-4, CX3CL1/fractalkine, neurotrophin 4 oncostatin-M, pulmonary and activation-regulated chemokine/CCL18, and transforming growth factor B3. These results support an unanticipated role of cystatin D in the cell nucleus, controlling the transcription of specific genes involved in crucial cellular functions, which may mediate its protective action in colon cancer.es_ES
dc.description.sponsorshipThis work was supported by Spanish Ministry of Economy and Competitiveness-Fondo Europeo de Desarrollo Regional (FEDER) Grant SAF2013-43468-R, Comunidad de Madrid Grant Colomics2 S2010/BMD-2344, and FEDER-Instituto de Salud Carlos III Grant RD12/0036/0021.es_ES
dc.language.isoenges_ES
dc.publisherAmerican Society for Biochemistry and Molecular Biologyes_ES
dc.relationMINECO/ICTI203-2016/SAF2013-43468-R-
dc.relationS2010/BMD-2344/Colomics2es_ES
dc.relation.isversionofPublisher's version-
dc.rightsopenAccesses_ES
dc.subjectColon canceres_ES
dc.subjectCysteine proteasees_ES
dc.subjectCytokinees_ES
dc.subjectGene expressiones_ES
dc.subjectProtease inhibitores_ES
dc.titleCystatin D locates in the nucleus at sites of active transcription and modulates gene and protein expressiones_ES
dc.typeartículoes_ES
dc.identifier.doi10.1074/jbc.M115.660175-
dc.description.peerreviewedPeer reviewedes_ES
dc.relation.publisherversionhttp://dx.doi.org/10.1074/jbc.M115.660175es_ES
dc.identifier.e-issn1083-351X-
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.contributor.funderComunidad de Madrides_ES
dc.contributor.funderEuropean Commissiones_ES
dc.contributor.funderInstituto de Salud Carlos IIIes_ES
dc.relation.csices_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100003329es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100000780es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100004587es_ES
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