A chimeric cyclic interferon-alpha2b peptide induces apoptosis by sequential activation of phosphatidyl inositol 3-kinase, protein kinase Cdelta and p38 MAP kinase

Autores
Blank, Viviana Claudia; Bertucci, Lucila; Furmento, Verónica Alejandra; Peña, Clara; Marino, Veronica Julieta; Roguin, Leonor Patricia
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We have previously demonstrated that tyrosine phosphorylation of STAT1/3 and p38 mitogen-activated protein kinase (p38 MAPK) activation are involved in the apoptotic response triggered by a chimeric cyclic peptide of the interferon-alpha2b (IFN-alpha2b) in WISH cells. Since the peptide also induced serine phosphorylation of STAT proteins, in the present study we examined the kinase involved in serine STAT1 phosphorylation and the signaling effectors acting upstream such activation. We first found that p38 MAPK is involved in serine STAT1 phosphorylation, since a reduction of phophoserine-STAT1 levels was evident after incubating WISH cells with cyclic peptide in the presence of a p38 pharmacological inhibitor or a dominant-negative p38 mutant. Next, we demonstrated that the peptide induced activation of protein kinase Cdelta (PKCdelta). Based on this finding, the role of this kinase was then evaluated. After incubating WISH cells with a PKCdelta inhibitor or after decreasing PKCdelta expression levels by RNA interference, both peptide-induced serine STAT1 and p38 phosphorylation levels were significantly decreased, indicating that PKCdelta functions as an upstream regulator of p38. We also showed that PKCdelta and p38 activation stimulated by the peptide was inhibited by a specific pharmacological inhibitor of phosphatidylinositol 3-kinase (PI3K) or by a dominant-negative p85 PI3K-regulatory subunit, suggesting that PI3K is upstream in the signaling cascade. In addition, the role of PI3K and PKCdelta in cyclic peptide-induced apoptosis was examined. Both signaling effectors were found to regulate the antiproliferative activity and the apoptotic response triggered by the cyclic peptide in WISH cells. In conclusion, we herein demonstrated that STAT1 serine phosphorylation is mediated by the sequential activation of PI3K, PKCdelta and p38 MAPK. This signaling cascade contributes to the antitumor effect induced by the chimeric IFN-alpha2b cyclic peptide in WISH cells.
Fil: Blank, Viviana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina
Fil: Bertucci, Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina
Fil: Furmento, Verónica Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina
Fil: Peña, Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina
Fil: Marino, Veronica Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina
Fil: Roguin, Leonor Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina
Materia
Cyclic Peptide
Mapk
Pi3k
Interferon Alpha
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/8376
Acceder
id CONICETDig_fcca5eb4b9ef04c3272fcfa3085b3249
oai_identifier_str oai:ri.conicet.gov.ar:11336/8376
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A chimeric cyclic interferon-alpha2b peptide induces apoptosis by sequential activation of phosphatidyl inositol 3-kinase, protein kinase Cdelta and p38 MAP kinaseBlank, Viviana ClaudiaBertucci, LucilaFurmento, Verónica AlejandraPeña, ClaraMarino, Veronica JulietaRoguin, Leonor PatriciaCyclic PeptideMapkPi3kInterferon Alphahttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1We have previously demonstrated that tyrosine phosphorylation of STAT1/3 and p38 mitogen-activated protein kinase (p38 MAPK) activation are involved in the apoptotic response triggered by a chimeric cyclic peptide of the interferon-alpha2b (IFN-alpha2b) in WISH cells. Since the peptide also induced serine phosphorylation of STAT proteins, in the present study we examined the kinase involved in serine STAT1 phosphorylation and the signaling effectors acting upstream such activation. We first found that p38 MAPK is involved in serine STAT1 phosphorylation, since a reduction of phophoserine-STAT1 levels was evident after incubating WISH cells with cyclic peptide in the presence of a p38 pharmacological inhibitor or a dominant-negative p38 mutant. Next, we demonstrated that the peptide induced activation of protein kinase Cdelta (PKCdelta). Based on this finding, the role of this kinase was then evaluated. After incubating WISH cells with a PKCdelta inhibitor or after decreasing PKCdelta expression levels by RNA interference, both peptide-induced serine STAT1 and p38 phosphorylation levels were significantly decreased, indicating that PKCdelta functions as an upstream regulator of p38. We also showed that PKCdelta and p38 activation stimulated by the peptide was inhibited by a specific pharmacological inhibitor of phosphatidylinositol 3-kinase (PI3K) or by a dominant-negative p85 PI3K-regulatory subunit, suggesting that PI3K is upstream in the signaling cascade. In addition, the role of PI3K and PKCdelta in cyclic peptide-induced apoptosis was examined. Both signaling effectors were found to regulate the antiproliferative activity and the apoptotic response triggered by the cyclic peptide in WISH cells. In conclusion, we herein demonstrated that STAT1 serine phosphorylation is mediated by the sequential activation of PI3K, PKCdelta and p38 MAPK. This signaling cascade contributes to the antitumor effect induced by the chimeric IFN-alpha2b cyclic peptide in WISH cells.Fil: Blank, Viviana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Bertucci, Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Furmento, Verónica Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Peña, Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Marino, Veronica Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Roguin, Leonor Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaElsevier2013-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/8376Blank, Viviana Claudia; Bertucci, Lucila; Furmento, Verónica Alejandra; Peña, Clara; Marino, Veronica Julieta; et al.; A chimeric cyclic interferon-alpha2b peptide induces apoptosis by sequential activation of phosphatidyl inositol 3-kinase, protein kinase Cdelta and p38 MAP kinase; Elsevier; Experimental Cell Research; 319; 10; 4-2013; 1471-14810014-4827enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0014482713001481info:eu-repo/semantics/altIdentifier/doi/10.1016/j.yexcr.2013.02.024info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:16:21Zoai:ri.conicet.gov.ar:11336/8376instacron: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:34982025-10-22 12:16:21.867CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A chimeric cyclic interferon-alpha2b peptide induces apoptosis by sequential activation of phosphatidyl inositol 3-kinase, protein kinase Cdelta and p38 MAP kinase
title A chimeric cyclic interferon-alpha2b peptide induces apoptosis by sequential activation of phosphatidyl inositol 3-kinase, protein kinase Cdelta and p38 MAP kinase
spellingShingle A chimeric cyclic interferon-alpha2b peptide induces apoptosis by sequential activation of phosphatidyl inositol 3-kinase, protein kinase Cdelta and p38 MAP kinase
Blank, Viviana Claudia
Cyclic Peptide
Mapk
Pi3k
Interferon Alpha
title_short A chimeric cyclic interferon-alpha2b peptide induces apoptosis by sequential activation of phosphatidyl inositol 3-kinase, protein kinase Cdelta and p38 MAP kinase
title_full A chimeric cyclic interferon-alpha2b peptide induces apoptosis by sequential activation of phosphatidyl inositol 3-kinase, protein kinase Cdelta and p38 MAP kinase
title_fullStr A chimeric cyclic interferon-alpha2b peptide induces apoptosis by sequential activation of phosphatidyl inositol 3-kinase, protein kinase Cdelta and p38 MAP kinase
title_full_unstemmed A chimeric cyclic interferon-alpha2b peptide induces apoptosis by sequential activation of phosphatidyl inositol 3-kinase, protein kinase Cdelta and p38 MAP kinase
title_sort A chimeric cyclic interferon-alpha2b peptide induces apoptosis by sequential activation of phosphatidyl inositol 3-kinase, protein kinase Cdelta and p38 MAP kinase
dc.creator.none.fl_str_mv Blank, Viviana Claudia
Bertucci, Lucila
Furmento, Verónica Alejandra
Peña, Clara
Marino, Veronica Julieta
Roguin, Leonor Patricia
author Blank, Viviana Claudia
author_facet Blank, Viviana Claudia
Bertucci, Lucila
Furmento, Verónica Alejandra
Peña, Clara
Marino, Veronica Julieta
Roguin, Leonor Patricia
author_role author
author2 Bertucci, Lucila
Furmento, Verónica Alejandra
Peña, Clara
Marino, Veronica Julieta
Roguin, Leonor Patricia
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Cyclic Peptide
Mapk
Pi3k
Interferon Alpha
topic Cyclic Peptide
Mapk
Pi3k
Interferon Alpha
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv We have previously demonstrated that tyrosine phosphorylation of STAT1/3 and p38 mitogen-activated protein kinase (p38 MAPK) activation are involved in the apoptotic response triggered by a chimeric cyclic peptide of the interferon-alpha2b (IFN-alpha2b) in WISH cells. Since the peptide also induced serine phosphorylation of STAT proteins, in the present study we examined the kinase involved in serine STAT1 phosphorylation and the signaling effectors acting upstream such activation. We first found that p38 MAPK is involved in serine STAT1 phosphorylation, since a reduction of phophoserine-STAT1 levels was evident after incubating WISH cells with cyclic peptide in the presence of a p38 pharmacological inhibitor or a dominant-negative p38 mutant. Next, we demonstrated that the peptide induced activation of protein kinase Cdelta (PKCdelta). Based on this finding, the role of this kinase was then evaluated. After incubating WISH cells with a PKCdelta inhibitor or after decreasing PKCdelta expression levels by RNA interference, both peptide-induced serine STAT1 and p38 phosphorylation levels were significantly decreased, indicating that PKCdelta functions as an upstream regulator of p38. We also showed that PKCdelta and p38 activation stimulated by the peptide was inhibited by a specific pharmacological inhibitor of phosphatidylinositol 3-kinase (PI3K) or by a dominant-negative p85 PI3K-regulatory subunit, suggesting that PI3K is upstream in the signaling cascade. In addition, the role of PI3K and PKCdelta in cyclic peptide-induced apoptosis was examined. Both signaling effectors were found to regulate the antiproliferative activity and the apoptotic response triggered by the cyclic peptide in WISH cells. In conclusion, we herein demonstrated that STAT1 serine phosphorylation is mediated by the sequential activation of PI3K, PKCdelta and p38 MAPK. This signaling cascade contributes to the antitumor effect induced by the chimeric IFN-alpha2b cyclic peptide in WISH cells.
Fil: Blank, Viviana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina
Fil: Bertucci, Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina
Fil: Furmento, Verónica Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina
Fil: Peña, Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina
Fil: Marino, Veronica Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina
Fil: Roguin, Leonor Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina
description We have previously demonstrated that tyrosine phosphorylation of STAT1/3 and p38 mitogen-activated protein kinase (p38 MAPK) activation are involved in the apoptotic response triggered by a chimeric cyclic peptide of the interferon-alpha2b (IFN-alpha2b) in WISH cells. Since the peptide also induced serine phosphorylation of STAT proteins, in the present study we examined the kinase involved in serine STAT1 phosphorylation and the signaling effectors acting upstream such activation. We first found that p38 MAPK is involved in serine STAT1 phosphorylation, since a reduction of phophoserine-STAT1 levels was evident after incubating WISH cells with cyclic peptide in the presence of a p38 pharmacological inhibitor or a dominant-negative p38 mutant. Next, we demonstrated that the peptide induced activation of protein kinase Cdelta (PKCdelta). Based on this finding, the role of this kinase was then evaluated. After incubating WISH cells with a PKCdelta inhibitor or after decreasing PKCdelta expression levels by RNA interference, both peptide-induced serine STAT1 and p38 phosphorylation levels were significantly decreased, indicating that PKCdelta functions as an upstream regulator of p38. We also showed that PKCdelta and p38 activation stimulated by the peptide was inhibited by a specific pharmacological inhibitor of phosphatidylinositol 3-kinase (PI3K) or by a dominant-negative p85 PI3K-regulatory subunit, suggesting that PI3K is upstream in the signaling cascade. In addition, the role of PI3K and PKCdelta in cyclic peptide-induced apoptosis was examined. Both signaling effectors were found to regulate the antiproliferative activity and the apoptotic response triggered by the cyclic peptide in WISH cells. In conclusion, we herein demonstrated that STAT1 serine phosphorylation is mediated by the sequential activation of PI3K, PKCdelta and p38 MAPK. This signaling cascade contributes to the antitumor effect induced by the chimeric IFN-alpha2b cyclic peptide in WISH cells.
publishDate 2013
dc.date.none.fl_str_mv 2013-04
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/11336/8376
Blank, Viviana Claudia; Bertucci, Lucila; Furmento, Verónica Alejandra; Peña, Clara; Marino, Veronica Julieta; et al.; A chimeric cyclic interferon-alpha2b peptide induces apoptosis by sequential activation of phosphatidyl inositol 3-kinase, protein kinase Cdelta and p38 MAP kinase; Elsevier; Experimental Cell Research; 319; 10; 4-2013; 1471-1481
0014-4827
url http://hdl.handle.net/11336/8376
identifier_str_mv Blank, Viviana Claudia; Bertucci, Lucila; Furmento, Verónica Alejandra; Peña, Clara; Marino, Veronica Julieta; et al.; A chimeric cyclic interferon-alpha2b peptide induces apoptosis by sequential activation of phosphatidyl inositol 3-kinase, protein kinase Cdelta and p38 MAP kinase; Elsevier; Experimental Cell Research; 319; 10; 4-2013; 1471-1481
0014-4827
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0014482713001481
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.yexcr.2013.02.024
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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
_version_ 1846782583418912768
score 12.982451

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