title: Cellular localization of human p53 expressed in the yeast Saccharomyces cerevisiae: effect of NLSI deletion.
abstract: The tumor suppressor p53 plays a central role in the regulation of cellular growth and apoptosis. In Saccharomyces cerevisiae, over-expression of the human wtp53 leads to growth inhibition and cell death on minimal medium. In the present work, we showed that deletion of the nuclear localization signal (NLSI) of p53 restores the yeast growth. In this heterologous context, the level of p53∆NLSI was low and the protein mainly located in the cytoplasm while the wtp53 was observed in both the cytoplasmic and nuclear compartments. Interestingly, the wtp53 protein was observed in the mitochondria, whereas the p53∆NLSI protein failed to localize in mitochondria. Moreover, mitochondrial morphology defect and release of cytochrome c in the cytosol were noticed only in the yeast strain expressing the wtp53. In conclusion, our results provide evidence that the human wtp53 is active in S. cerevisiae probably through dependent and independent transcriptional mechanisms leading to cell death. The deletion of the NLSI sequence decreases p53 nuclear translocation as well as its mitochondrial localization and consequently its effect on yeast growth.
authors.affiliation: University of Sfax, 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.
authors.forename: Salma
authors.initials: S
authors.lastname: Abdelmoula-Souissi
authors.forename: Agnès
authors.initials: A
authors.lastname: Delahodde
authors.forename: Monique
authors.initials: M
authors.lastname: Bolotin-Fukuhara
authors.forename: Ali
authors.initials: A
authors.lastname: Gargouri
authors.forename: Raja
authors.initials: R
authors.lastname: Mokdad-Gargouri
mesh_terms: D015153:Blotting, Western; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019913:Nuclear Localization Signals / Q000235:genetics*; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D017384:Sequence Deletion / Q000235:genetics*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D019913:Nuclear Localization Signals; D016159:Tumor Suppressor Protein p53; D004247:DNA; D005947:Glucose