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Originally published In Press as doi:10.1074/jbc.M708703200 on May 12, 2008

J. Biol. Chem., Vol. 283, Issue 28, 19714-19729, July 11, 2008
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Hsf-1 and POB1 Induce Drug Sensitivity and Apoptosis by Inhibiting Ralbp1*

Sharad S. Singhal, Sushma Yadav, Kenneth Drake, Jyotsana Singhal, and Sanjay Awasthi1

From the Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, Texas 76107-2699

Hsf-1 (heat shock factor-1) is a transcription factor that is known to regulate cellular heat shock response through its binding with the multispecific transporter protein, Ralbp1. Results of present studies demonstrate that Hsf-1 causes specific and saturable inhibition of the transport activity of Ralbp1 and that the combination of Hsf-1 and POB1 causes nearly complete inhibition through specific bindings with Ralbp1. Augmentation of cellular levels of Hsf-1 and POB1 caused dramatic apoptosis in non-small cell lung cancer cell line H358 through Ralbp1 inhibition. These findings indicate a novel model for mutual regulation of Hsf-1 and Ralbp1 through Ralbp1-mediated sequestration of Hsf-1 in the cellular cytoskeleton and Hsf-1-mediated inhibition of the transport activity of membrane-bound Ralbp1.


Received for publication, October 22, 2007 , and in revised form, May 1, 2008.

* This work was supported, in whole or in part, by National Institutes of Health Grants CA 77495 and CA 104661 (to S. A.). This work was also supported by the Cancer Research Foundation of North Texas (to S. S. S. and S. Y.), the Institute for Cancer Research, and the Joe and Jessie Crump Fund for Medical Education (to S. S. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 To whom correspondence should be addressed: Dept. of Molecular Biology and Immunology, 3500 Camp Bowie Blvd., EAD Rm. 552, University of North Texas Health Science Center, Fort Worth, TX 76107-2699. Tel.: 817-735-0459; Fax: 817-735-2118; E-mail: sawasthi{at}hsc.unt.edu.


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This article has been cited by other articles:


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[Abstract] [Full Text] [PDF]




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