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The Journal of Biological Chemistry
Year: 2008  |  Volume: 283  |  Issue: 28  |  Page No.: 19714 - 19729

Hsf-1 and POB1 Induce Drug Sensitivity and Apoptosis by Inhibiting Ralbp1

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

Abstract: 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.

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