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dc.contributor.author
Ceballos Mancini, María Paula
dc.contributor.author
Parody, Juan Pablo
dc.contributor.author
Quiroga, Ariel Dario
dc.contributor.author
Casella, María Laura
dc.contributor.author
Frances, Daniel Eleazar Antonio
dc.contributor.author
Larocca, Maria Cecilia
dc.contributor.author
Carnovale, Cristina Ester
dc.contributor.author
Alvarez, María de Luján
dc.contributor.author
Carrillo, Maria Cristina
dc.date.available
2016-06-08T13:47:12Z
dc.date.issued
2014-11
dc.identifier.citation
Ceballos Mancini, María Paula; Parody, Juan Pablo; Quiroga, Ariel Dario; Casella, María Laura; Frances, Daniel Eleazar Antonio; et al.; FoxO3a nuclear localization and its association with beta-catenin and Smads in IFN-alfa-treated hepatocellular carcinoma cell lines; Mary Ann Liebert Inc; Journal of Interferon and Cytokine Research; 34; 11; 11-2014; 858-869
dc.identifier.issn
1079-9907
dc.identifier.uri
http://hdl.handle.net/11336/6100
dc.description.abstract
Interferon-a2b (IFN-a2b) reduces proliferation and increases apoptosis in hepatocellular carcinoma cells by decreasing b-catenin/TCF4/Smads interaction. Forkhead box O-class 3a (FoxO3a) participates in proliferation and apoptosis and interacts with b-catenin and Smads. FoxO3a is inhibited by Akt, IkB kinase b (IKKb), and extracellular-signal-regulated kinase (Erk), which promote FoxO3a sequestration in the cytosol, and accumulates in the nucleus upon phosphorylation by c-Jun N-terminal kinase ( JNK) and p38 mitogen-activated kinase (p38 MAPK). We analyzed FoxO3a subcellular localization, the participating kinases, FoxO3a/b-catenin/ Smads association, and FoxO3a target gene expression in IFN-a2b-stimulated HepG2/C3A and Huh7 cells. Total FoxO3a and Akt-phosphorylated FoxO3a levels decreased in the cytosol, whereas total FoxO3a levels increased in the nucleus upon IFN-a2b stimulus. IFN-a2b reduced Akt, IKKb, and Erk activation, and increased JNK and p38 MAPK activation. p38 MAPK inhibition blocked IFN-a2b-induced FoxO3a nuclear localization. IFN-a2b enhanced FoxO3a association with b-catenin and Smad2/3/7. Two-step coimmunoprecipitation experiments suggest that these proteins coexist in the same complex. The expression of several FoxO3a target genes increased with IFN-a2b. FoxO3a knockdown prevented the induction of these genes, suggesting that FoxO3a acts as mediator of IFN-a2b action. Results suggest a b-catenin/Smads switch from TCF4 to FoxO3a. Such events would contribute to the IFN-a2b-mediated effects on cellular proliferation and apoptosis. These results demonstrate new
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Mary Ann Liebert Inc
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Foxo3a
dc.subject
Beta Catenin
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Smads
dc.subject
Hcc
dc.subject.classification
Fisiología
dc.subject.classification
Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
FoxO3a nuclear localization and its association with beta-catenin and Smads in IFN-alfa-treated hepatocellular carcinoma cell lines
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-06-01T14:02:58Z
dc.journal.volume
34
dc.journal.number
11
dc.journal.pagination
858-869
dc.journal.pais
Estados Unidos
dc.journal.ciudad
New York
dc.description.fil
Fil: Ceballos Mancini, María Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.description.fil
Fil: Parody, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.description.fil
Fil: Quiroga, Ariel Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.description.fil
Fil: Casella, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.description.fil
Fil: Frances, Daniel Eleazar Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.description.fil
Fil: Larocca, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.description.fil
Fil: Carnovale, Cristina Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.description.fil
Fil: Alvarez, María de Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.description.fil
Fil: Carrillo, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.journal.title
Journal of Interferon and Cytokine Research
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/10.1089/jir.2013.0124
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1089/jir.2013.0124
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://online.liebertpub.com/doi/abs/10.1089/jir.2013.0124
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/pmid/PMC4217017
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4217017/


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