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https://hdl.handle.net/1822/16068
Título: | 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(es): | Coutinho, Isabel Pereira, Clara Pereira, Gil Gonçalves, Jorge Côrte-Real, Manuela Saraiva, Lucília |
Palavras-chave: | P53 PKC isoforms Apoptosis Transcription Mitochondria Yeast |
Data: | Mai-2011 |
Editora: | Elsevier 1 |
Revista: | Experimental Cell Research |
Resumo(s): | 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. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/16068 |
DOI: | 10.1016/j.yexcr.2011.02.007 |
ISSN: | 0014-4827 |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | DBio - Artigos/Papers |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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Coutinho et al. 2011 post-print.pdf | post-print | 560,52 kB | Adobe PDF | Ver/Abrir |