Expression of the human tumor suppressor p53 induces cell death in Pichia pastoris

Authors

  • Salma Abdelmoula-Souissi,

    1. Laboratoire de Valorisation de la Biomasse et Production de Protéines chez les Eucaryotes, Centre de Biotechnologie de Sfax, University of Sfax, Sfax, Tunisia
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  • Imed Mabrouk,

    1. Laboratoire de Valorisation de la Biomasse et Production de Protéines chez les Eucaryotes, Centre de Biotechnologie de Sfax, University of Sfax, Sfax, Tunisia
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  • Ali Gargouri,

    1. Laboratoire de Valorisation de la Biomasse et Production de Protéines chez les Eucaryotes, Centre de Biotechnologie de Sfax, University of Sfax, Sfax, Tunisia
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  • Raja Mokdad-Gargouri

    Corresponding author
    • Laboratoire de Valorisation de la Biomasse et Production de Protéines chez les Eucaryotes, Centre de Biotechnologie de Sfax, University of Sfax, Sfax, Tunisia
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Correspondence: Raja Mokdad-Gargouri, Laboratoire de Valorisation de la Biomasse et Production de Protéines chez les Eucaryotes, Centre de Biotechnologie de Sfax, Route Sidi Mansour, BP 1177 3018 Sfax, Tunisia. Tel./fax: +216 74 874 449; e-mail: raja.gargouri@cbs.rnrt.tn

Abstract

The human tumor suppressor p53 is known as guardian of genome because of its involvement in many signals related to cell life or death. In this work, we report that human p53 induces cell death in the yeast Pichia pastoris. We showed a growth inhibition effect, which increased with the p53 protein expression level in recombinant Muts (methanol utilization slow) strain of Pichia. However, no effect of p53 was observed in recombinant strain of Mut+ (methanol utilization plus) phenotype. Interestingly, human p53 induces cell death in recombinant strains Muts with characteristic markers of apoptosis such as DNA fragmentation, exposure of phosphatidylserine, and reactive oxygen species generation. Taken together, our results strongly suggest that human p53 is biologically active in this heterologous context. Thus, we propose that P. pastoris could be a useful tool to better understand the biological function of human p53.

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