FoxO3a nuclear localization and its association with beta-catenin and Smads in IFN-alfa-treated hepatocellular carcinoma cell lines
- Autores
- Ceballos Mancini, María Paula; Parody, Juan Pablo; Quiroga, Ariel Dario; Casella, María Laura; Frances, Daniel Eleazar Antonio; Larocca, Maria Cecilia; Carnovale, Cristina Ester; Alvarez, María de Luján; Carrillo, Maria Cristina
- Año de publicación
- 2014
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- 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
Fil: Ceballos Mancini, María Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Parody, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Quiroga, Ariel Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Casella, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Frances, Daniel Eleazar Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Larocca, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Carnovale, Cristina Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Alvarez, María de Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Carrillo, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina - Materia
-
Foxo3a
Beta Catenin
Smads
Hcc - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/6100
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oai:ri.conicet.gov.ar:11336/6100 |
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FoxO3a nuclear localization and its association with beta-catenin and Smads in IFN-alfa-treated hepatocellular carcinoma cell linesCeballos Mancini, María PaulaParody, Juan PabloQuiroga, Ariel DarioCasella, María LauraFrances, Daniel Eleazar AntonioLarocca, Maria CeciliaCarnovale, Cristina EsterAlvarez, María de LujánCarrillo, Maria CristinaFoxo3aBeta CateninSmadsHcchttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Interferon-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 newFil: Ceballos Mancini, María Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaFil: Parody, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaFil: Quiroga, Ariel Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaFil: Casella, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaFil: Frances, Daniel Eleazar Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaFil: Larocca, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaFil: Carnovale, Cristina Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaFil: Alvarez, María de Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaFil: Carrillo, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaMary Ann Liebert Inc2014-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/6100Ceballos 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; 858-8691079-9907enginfo:eu-repo/semantics/altIdentifier/doi/10.1089/jir.2013.0124info:eu-repo/semantics/altIdentifier/url/http://online.liebertpub.com/doi/abs/10.1089/jir.2013.0124info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:41:01Zoai:ri.conicet.gov.ar:11336/6100instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:41:02.176CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
FoxO3a nuclear localization and its association with beta-catenin and Smads in IFN-alfa-treated hepatocellular carcinoma cell lines |
title |
FoxO3a nuclear localization and its association with beta-catenin and Smads in IFN-alfa-treated hepatocellular carcinoma cell lines |
spellingShingle |
FoxO3a nuclear localization and its association with beta-catenin and Smads in IFN-alfa-treated hepatocellular carcinoma cell lines Ceballos Mancini, María Paula Foxo3a Beta Catenin Smads Hcc |
title_short |
FoxO3a nuclear localization and its association with beta-catenin and Smads in IFN-alfa-treated hepatocellular carcinoma cell lines |
title_full |
FoxO3a nuclear localization and its association with beta-catenin and Smads in IFN-alfa-treated hepatocellular carcinoma cell lines |
title_fullStr |
FoxO3a nuclear localization and its association with beta-catenin and Smads in IFN-alfa-treated hepatocellular carcinoma cell lines |
title_full_unstemmed |
FoxO3a nuclear localization and its association with beta-catenin and Smads in IFN-alfa-treated hepatocellular carcinoma cell lines |
title_sort |
FoxO3a nuclear localization and its association with beta-catenin and Smads in IFN-alfa-treated hepatocellular carcinoma cell lines |
dc.creator.none.fl_str_mv |
Ceballos Mancini, María Paula Parody, Juan Pablo Quiroga, Ariel Dario Casella, María Laura Frances, Daniel Eleazar Antonio Larocca, Maria Cecilia Carnovale, Cristina Ester Alvarez, María de Luján Carrillo, Maria Cristina |
author |
Ceballos Mancini, María Paula |
author_facet |
Ceballos Mancini, María Paula Parody, Juan Pablo Quiroga, Ariel Dario Casella, María Laura Frances, Daniel Eleazar Antonio Larocca, Maria Cecilia Carnovale, Cristina Ester Alvarez, María de Luján Carrillo, Maria Cristina |
author_role |
author |
author2 |
Parody, Juan Pablo Quiroga, Ariel Dario Casella, María Laura Frances, Daniel Eleazar Antonio Larocca, Maria Cecilia Carnovale, Cristina Ester Alvarez, María de Luján Carrillo, Maria Cristina |
author2_role |
author author author author author author author author |
dc.subject.none.fl_str_mv |
Foxo3a Beta Catenin Smads Hcc |
topic |
Foxo3a Beta Catenin Smads Hcc |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
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 Fil: Ceballos Mancini, María Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina Fil: Parody, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina Fil: Quiroga, Ariel Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina Fil: Casella, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina Fil: Frances, Daniel Eleazar Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina Fil: Larocca, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina Fil: Carnovale, Cristina Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina Fil: Alvarez, María de Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina Fil: Carrillo, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina |
description |
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 |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-11 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/6100 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 1079-9907 |
url |
http://hdl.handle.net/11336/6100 |
identifier_str_mv |
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 1079-9907 |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1089/jir.2013.0124 info:eu-repo/semantics/altIdentifier/url/http://online.liebertpub.com/doi/abs/10.1089/jir.2013.0124 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Mary Ann Liebert Inc |
publisher.none.fl_str_mv |
Mary Ann Liebert Inc |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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1846082904967348224 |
score |
13.22299 |