Distinct regulation of p53-mediated apoptosis by protein kinase calpha, delta, epsilon and zeta: evidence in yeast for transcription-dependent and -independent p53 apoptotic mechanisms
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/16068 |
Resumo: | The role of individual protein kinase C (PKC) isoforms in the regulation of p53- mediated apoptosis is still uncertain. Using yeast cells co-expressing the human wild-type p53 and a single mammalian PKCa, d, e or z, we showed a differential regulation of p53- mediated apoptosis by these PKC isoforms. Whereas PKCa and z had no effect on p53 activity, PKCd and e stimulated a p53-mediated mitochondria-dependent apoptosis. Moreover, using pifithrin-a and -m, selective inhibitors of p53 transcriptional activity and mitochondrial p53 translocation, respectively, we showed the activation of a transcriptiondependent and -independent p53-mediated apoptosis by PKCd and e. The activation of mitochondrial p53 translocation by PKCd and e was further confirmed by immunofluorescence and Western blot analysis. Together, this work reveals the conservation in yeast of functional transcriptiondependent and -independent p53 apoptotic mechanisms. Furthermore, it gives mechanistic insights about the regulation of p53-mediated apoptosis by PKCd and e through modulation of p53 transcriptional activity and of its translocation to mitochondria. Finally, it underscores a major role of PKCd and e as positive regulators of p53-mediated apoptosis, and therefore as promising therapeutic targets in cancer. |
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Distinct regulation of p53-mediated apoptosis by protein kinase calpha, delta, epsilon and zeta: evidence in yeast for transcription-dependent and -independent p53 apoptotic mechanismsP53PKC isoformsApoptosisTranscriptionMitochondriaYeastScience & TechnologyThe role of individual protein kinase C (PKC) isoforms in the regulation of p53- mediated apoptosis is still uncertain. Using yeast cells co-expressing the human wild-type p53 and a single mammalian PKCa, d, e or z, we showed a differential regulation of p53- mediated apoptosis by these PKC isoforms. Whereas PKCa and z had no effect on p53 activity, PKCd and e stimulated a p53-mediated mitochondria-dependent apoptosis. Moreover, using pifithrin-a and -m, selective inhibitors of p53 transcriptional activity and mitochondrial p53 translocation, respectively, we showed the activation of a transcriptiondependent and -independent p53-mediated apoptosis by PKCd and e. The activation of mitochondrial p53 translocation by PKCd and e was further confirmed by immunofluorescence and Western blot analysis. Together, this work reveals the conservation in yeast of functional transcriptiondependent and -independent p53 apoptotic mechanisms. Furthermore, it gives mechanistic insights about the regulation of p53-mediated apoptosis by PKCd and e through modulation of p53 transcriptional activity and of its translocation to mitochondria. Finally, it underscores a major role of PKCd and e as positive regulators of p53-mediated apoptosis, and therefore as promising therapeutic targets in cancer.REQUIMTE/CEQUP, FCT (I&D No 8/94; PTDC/ SAU-FAR/110848/2009), POCTI (QCA III), FEDER and U.Porto/ Santander Totta. I. Coutinho is recipient of a PhD fellowship from FCT (SFRH/BD/36066/2007). C. Pereira is recipient of a Post-Doctoral fellowship from FCT (SFRH/BPD/44209/2008).ElsevierUniversidade do MinhoCoutinho, IsabelPereira, ClaraPereira, GilGonçalves, JorgeCôrte-Real, ManuelaSaraiva, Lucília2011-052011-05-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/16068eng0014-482710.1016/j.yexcr.2011.02.00721338602info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:16:25Zoai:repositorium.sdum.uminho.pt:1822/16068Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:08:57.542887Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Distinct regulation of p53-mediated apoptosis by protein kinase calpha, delta, epsilon and zeta: evidence in yeast for transcription-dependent and -independent p53 apoptotic mechanisms |
title |
Distinct regulation of p53-mediated apoptosis by protein kinase calpha, delta, epsilon and zeta: evidence in yeast for transcription-dependent and -independent p53 apoptotic mechanisms |
spellingShingle |
Distinct regulation of p53-mediated apoptosis by protein kinase calpha, delta, epsilon and zeta: evidence in yeast for transcription-dependent and -independent p53 apoptotic mechanisms Coutinho, Isabel P53 PKC isoforms Apoptosis Transcription Mitochondria Yeast Science & Technology |
title_short |
Distinct regulation of p53-mediated apoptosis by protein kinase calpha, delta, epsilon and zeta: evidence in yeast for transcription-dependent and -independent p53 apoptotic mechanisms |
title_full |
Distinct regulation of p53-mediated apoptosis by protein kinase calpha, delta, epsilon and zeta: evidence in yeast for transcription-dependent and -independent p53 apoptotic mechanisms |
title_fullStr |
Distinct regulation of p53-mediated apoptosis by protein kinase calpha, delta, epsilon and zeta: evidence in yeast for transcription-dependent and -independent p53 apoptotic mechanisms |
title_full_unstemmed |
Distinct regulation of p53-mediated apoptosis by protein kinase calpha, delta, epsilon and zeta: evidence in yeast for transcription-dependent and -independent p53 apoptotic mechanisms |
title_sort |
Distinct regulation of p53-mediated apoptosis by protein kinase calpha, delta, epsilon and zeta: evidence in yeast for transcription-dependent and -independent p53 apoptotic mechanisms |
author |
Coutinho, Isabel |
author_facet |
Coutinho, Isabel Pereira, Clara Pereira, Gil Gonçalves, Jorge Côrte-Real, Manuela Saraiva, Lucília |
author_role |
author |
author2 |
Pereira, Clara Pereira, Gil Gonçalves, Jorge Côrte-Real, Manuela Saraiva, Lucília |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Coutinho, Isabel Pereira, Clara Pereira, Gil Gonçalves, Jorge Côrte-Real, Manuela Saraiva, Lucília |
dc.subject.por.fl_str_mv |
P53 PKC isoforms Apoptosis Transcription Mitochondria Yeast Science & Technology |
topic |
P53 PKC isoforms Apoptosis Transcription Mitochondria Yeast Science & Technology |
description |
The role of individual protein kinase C (PKC) isoforms in the regulation of p53- mediated apoptosis is still uncertain. Using yeast cells co-expressing the human wild-type p53 and a single mammalian PKCa, d, e or z, we showed a differential regulation of p53- mediated apoptosis by these PKC isoforms. Whereas PKCa and z had no effect on p53 activity, PKCd and e stimulated a p53-mediated mitochondria-dependent apoptosis. Moreover, using pifithrin-a and -m, selective inhibitors of p53 transcriptional activity and mitochondrial p53 translocation, respectively, we showed the activation of a transcriptiondependent and -independent p53-mediated apoptosis by PKCd and e. The activation of mitochondrial p53 translocation by PKCd and e was further confirmed by immunofluorescence and Western blot analysis. Together, this work reveals the conservation in yeast of functional transcriptiondependent and -independent p53 apoptotic mechanisms. Furthermore, it gives mechanistic insights about the regulation of p53-mediated apoptosis by PKCd and e through modulation of p53 transcriptional activity and of its translocation to mitochondria. Finally, it underscores a major role of PKCd and e as positive regulators of p53-mediated apoptosis, and therefore as promising therapeutic targets in cancer. |
publishDate |
2011 |
dc.date.none.fl_str_mv |
2011-05 2011-05-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/16068 |
url |
http://hdl.handle.net/1822/16068 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0014-4827 10.1016/j.yexcr.2011.02.007 21338602 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799132513949450240 |