Genetic analysis of p53 nuclear importation

Q. Li, R. R. Falsey, S. Gaitonde, V. Sotello, K. Kislin, J. D. Martinez

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

A key step in activation of the p53 tumor suppressor is its transport into the nucleus; however, despite intensive study of p53, the regulation of its subcellular localization is still poorly understood. Here we examined the p53 nuclear importation using a series of mutant cell lines that were resistant to the growth inhibitory effects of temperature-sensitive murine p53 (tsp53). Examination of the p53 subcellular localization in these cell lines showed that the protein was cytoplasmic in most of them. Using a digitonin-permeabilized cell in vitro nuclear import system, we show that cytosols from these cell lines do not support nuclear translocation of a p53 nuclear localization signal (NLS)-containing substrate protein, but promote nuclear localization of a SV40TAgNLS-containing substrate. Complementation assays and use of the mutant cells themselves in the in vitro assays demonstrate that both soluble and insoluble protein components are involved in p53 nuclear import. Collectively, our results suggest that there is a p53 NLS-selective nuclear import pathway and that both soluble and insoluble proteins are involved in its function.

Original languageEnglish (US)
Pages (from-to)7885-7893
Number of pages9
JournalOncogene
Volume26
Issue number57
DOIs
StatePublished - Dec 13 2007

Keywords

  • Mutant
  • Nuclear localization
  • Temperature sensitive
  • p53

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Li, Q., Falsey, R. R., Gaitonde, S., Sotello, V., Kislin, K., & Martinez, J. D. (2007). Genetic analysis of p53 nuclear importation. Oncogene, 26(57), 7885-7893. https://doi.org/10.1038/sj.onc.1210597