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Molecular and Cellular Biology, January 2006, p. 580-591, Vol. 26, No. 2
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.2.580-591.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Heat Shock-Independent Induction of Multidrug Resistance by Heat Shock Factor 1{dagger}

Thierry Tchénio,1* Marilyne Havard,1 Luis A. Martinez,2 and François Dautry1

Unité de Génétique Moléculaire et Intégrations des Fonctions Cellulaires, CNRS UPR1983, 7 rue Guy Moquet, BP8, 94801 Villejuif Cedex, France,1 Unité d'Oncogenèse, Différentiation, et Transduction du Signal, UPR9079, 7 rue Guy Moquet, BP8, 94801 Villejuif Cedex, France2

Received 11 July 2005/ Returned for modification 7 September 2005/ Accepted 19 October 2005

The screening of two different retroviral cDNA expression libraries to select genes that confer constitutive doxorubicin resistance has in both cases resulted in the isolation of the heat shock factor 1 (HSF1) transcription factor. We show that HSF1 induces a multidrug resistance phenotype that occurs in the absence of heat shock or cellular stress and is mediated at least in part through the constitutive activation of the multidrug resistance gene 1 (MDR-1). This drug resistance phenotype does not correlate with an increased expression of heat shock-responsive genes (heat shock protein genes, or HSPs). In addition, HSF1 mutants lacking HSP gene activation are also capable of conferring multidrug resistance, and only hypophosphorylated HSF1 complexes accumulate in transduced cells. Our results indicate that HSF1 can activate MDR-1 expression in a stress-independent manner that differs from the canonical heat shock-activated mechanism involved in HSP induction. We further provide evidence that the induction of MDR-1 expression occurs at a posttranscriptional level, revealing a novel undocumented role for hypophosphorylated HSF1 in posttranscriptional gene regulation.

* Corresponding author. Mailing address: CNRS-UPR1983, 7 rue Guy Moquet, BP8, 94801 Villejuif Cedex, France. Phone: 33 1 49 58 33 76. Fax: 33 1 49 58 33 81. E-mail: tchenio{at}infobiogen.fr.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, January 2006, p. 580-591, Vol. 26, No. 2
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.2.580-591.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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