A Small Molecule Inhibitor of Inducible Heat Shock Protein 70

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2009 Oct 13

PMID 19818706

Citations 238

Authors

J I-Ju Leu

Julia Pimkina

Amanda Frank

Maureen E Murphy

Donna L George

Affiliations

Soon will be listed here.

Abstract

The multifunctional, stress-inducible molecular chaperone HSP70 has important roles in aiding protein folding and maintaining protein homeostasis. HSP70 expression is elevated in many cancers, contributing to tumor cell survival and resistance to therapy. We have determined that a small molecule called 2-phenylethynesulfonamide (PES) interacts selectively with HSP70 and leads to a disruption of the association between HSP70 and several of its cochaperones and substrate proteins. Treatment of cultured tumor cells with PES promotes cell death that is associated with protein aggregation, impaired autophagy, and inhibition of lysosomal function. Moreover, this small molecule is able to suppress tumor development and enhance survival in a mouse model of Myc-induced lymphomagenesis. The data demonstrate that PES disrupts actions of HSP70 in multiple cell signaling pathways, offering an opportunity to better understand the diverse functions of this molecular chaperone and also to aid in the development of new cancer therapies.

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