Hsf1 is required for the nuclear translocation of p53 tumor suppressor

Qiang Li, Rebecca A. Feldman, Vijayababu M. Radhakrishnan, Steven Carey, Jesse D Martinez

Research output: Contribution to journalArticle

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Abstract

Although the p53 tumor suppressor is most frequently inactivated by genetic mutations, exclusion from the nucleus is also seen in human tumors. We have begun to examine p53 nuclear importation by isolating a series of mutant cells in which the temperature-sensitive murine p53Val135 mutant is sequestered in the cytoplasm. We previously showed that that three of them (ALTR12, ALTR19, and ALTR25) constituted a single complementation group. Here, we found that ALTR12 cells are more sensitive to heat stress than either ALTR19 or ALTR25 and that there was a complete lack of induction of Hsp70 in response to heat shock. Western blot analysis showed no expression of the Hsf1 transcription factor, and neither heat shock nor azetidine could induce p53 nuclear localization in ALTR12 cells but did in parental A1-5 cells. Suppression of Hsf1 in A1-5 cells with quercetin or an Hsf1 siRNA reduced p53 nuclear importation and inhibited p53-mediated activation of a p21 reporter. Most convincingly, p53 nuclear importation could be restored in ALTR12 cells by introducing an exogenous Hsf1 gene. Collectively, our result suggests that Hsf1 is required for p53 nuclear importation and activation and implies that heat shock factors play a role in the regulation of p53.

Original languageEnglish (US)
Pages (from-to)1138-1145
Number of pages8
JournalNeoplasia
Volume10
Issue number10
DOIs
StatePublished - Oct 2008

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Neoplasms
Hot Temperature
Heat-Shock Response
Quercetin
Small Interfering RNA
Shock
Cytoplasm
Western Blotting
Mutation
Temperature
Genes
azetidine
heat shock transcription factor

ASJC Scopus subject areas

  • Cancer Research

Cite this

Hsf1 is required for the nuclear translocation of p53 tumor suppressor. / Li, Qiang; Feldman, Rebecca A.; Radhakrishnan, Vijayababu M.; Carey, Steven; Martinez, Jesse D.

In: Neoplasia, Vol. 10, No. 10, 10.2008, p. 1138-1145.

Research output: Contribution to journalArticle

Li, Q, Feldman, RA, Radhakrishnan, VM, Carey, S & Martinez, JD 2008, 'Hsf1 is required for the nuclear translocation of p53 tumor suppressor', Neoplasia, vol. 10, no. 10, pp. 1138-1145. https://doi.org/10.1593/neo.08430
Li, Qiang ; Feldman, Rebecca A. ; Radhakrishnan, Vijayababu M. ; Carey, Steven ; Martinez, Jesse D. / Hsf1 is required for the nuclear translocation of p53 tumor suppressor. In: Neoplasia. 2008 ; Vol. 10, No. 10. pp. 1138-1145.
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