P53 is transported into the nucleus via an Hsf1-dependent nuclear localization mechanism

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Abstract

Loss of p53 function can occur through disruption of its ability to localize to the nucleus. Previously we showed through characterization a set of mutant cell lines that lacked the ability to import p53 into the nucleus that nuclear translocation of p53 appeared to be mechanistically different from that of the SV40 T-antigen (SV40TAg). Here we extend that work by examining nuclear importation of p53 and SV40TAg using both in vivo and in vitro assays for nuclear localization. We show that disruption of microtubule polymerization using colchicine suppresses nuclear localization of p53 but not of SV40TAg. We also show, for the first time, that the heat shock transcription factor (Hsf1), is required for establishment of the microtubule network in cells and for nuclear localization of p53. In contrast, SV40TAg does not interact with polymerized microtubules suggesting that it is transported into the nucleus through an alternative mechanism. Interestingly, lacking of Hsf1 expression and suppressing Hsf1 by siRNA also made cells more resistant to the cytotoxic effects of paclitaxel. Hence, loss of Hsf1 activity not only suppressed p53 function, but also led to reduced sensitivity to killing by drugs that target microtubules.

Original languageEnglish (US)
Pages (from-to)143-152
Number of pages10
JournalMolecular Carcinogenesis
Volume50
Issue number2
DOIs
StatePublished - Feb 2011

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Polyomavirus Transforming Antigens
Microtubules
Colchicine
Paclitaxel
Polymerization
Small Interfering RNA
Cell Line
Pharmaceutical Preparations

Keywords

  • Heat shock factor
  • Hsf1
  • Microtubules
  • Nuclear localization
  • P53

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

Cite this

P53 is transported into the nucleus via an Hsf1-dependent nuclear localization mechanism. / Li, Qiang; Martinez, Jesse D.

In: Molecular Carcinogenesis, Vol. 50, No. 2, 02.2011, p. 143-152.

Research output: Contribution to journalArticle

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