hGTSE-1 Expression Stimulates Cytoplasmic Localization of p53

Martin Monte, Roberta Benetti, Licio Collavin, Luigi Marchionni, Giannino Del Sal, Claudio Schneider

Research output: Contribution to journalArticle

Abstract

hGTSE-1 (human G2 and S phase-expressed-1) is a cell cycle-regulated protein mainly localized in the cytoplasm and apparently associated with the microtubules. hGTSE-1 is able to down-regulate levels and activity of the p53 tumor suppressor protein: it binds the C-terminal region of p53 and represses its ability to induce apoptosis after DNA damage. Here we report that, after DNA damage, hGTSE-1 becomes stabilized in a p53-independent way and accumulated in the nucleus. Further characterization of hGTSE-1 localization revealed increased nuclear staining in unstressed cells after treatment with the nuclear export inhibitor leptomycin B, or when a nuclear export signal (NES) located in its C-terminal region was mutated. Finally, we provide evidence that hGTSE-1 ectopic expression, in addition to p53 protein levels down-regulation, is able to enhance cytoplasmic localization of p53. Interestingly, NES-mutated hGTSE-1 accumulates in the nucleus, binds p53 but looses its ability to enhance cytoplasmic redistribution of p53 and to regulate p53 protein levels. Similarly, when wild type hGTSE-1 functions on p53 were analyzed in cells lacking Mdm2, it failed in regulating both p53 localization and protein levels, thus indicating that hGTSE-1 requires an intact NES and functional Mdm2 for the regulation of p53. Our results provide new insights into the mechanism of hGTSE-1 function, whereby its characterized nucleo-cytoplasmic shuttling ability is required to regulate p53.

Original languageEnglish (US)
Pages (from-to)11744-11752
Number of pages9
JournalJournal of Biological Chemistry
Volume279
Issue number12
DOIs
StatePublished - Mar 19 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Monte, M., Benetti, R., Collavin, L., Marchionni, L., Del Sal, G., & Schneider, C. (2004). hGTSE-1 Expression Stimulates Cytoplasmic Localization of p53. Journal of Biological Chemistry, 279(12), 11744-11752. https://doi.org/10.1074/jbc.M311123200