The role of heat shock proteins in regulating receptor signal transduction

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22 Scopus citations

Abstract

Heat shock proteins (Hsp) are a class of stress-inducible proteins that mainly act as molecular protein chaperones. This chaperone activity is diverse, including assisting in nascent protein folding and regulating client protein location and translocation within the cell. The main proteins within the Hsp family, particularly Hsp70 and Hsp90, also have a highly diverse and numerous set of protein clients, which when combined with the high expression levels of Hsp proteins (2%–6% of total protein content) establishes these molecules as “central regulators” of cell protein physiology. Among the client proteins, Hsps regulate numerous signal-transduction and receptor-regulatory kinases, and indeed directly regulate some receptors themselves. This also makes the Hsps, particularly Hsp90, central regulators of signal-transduction machinery, with important impacts on endogenous and drug ligand responses. Among these roles, Hsp90 in particular acts to maintain mature signaling kinases in a metastable conformation permissive for signaling activation. In this review, we will focus on the roles of the Hsps, with a special focus on Hsp90, in regulating receptor signaling and subsequent physiologic responses. We will also explore potential means to manipulate Hsp function to improve receptor-targeted therapies. Overall, Hsps are important regulators of receptor signaling that are receiving increasing interest and exploration, particularly as Hsp90 inhibitors progress toward clinical approval for the treatment of cancer. Understanding the complex interplay of Hsp regulation of receptor signaling may provide important avenues to improve patient treatment.

Original languageEnglish (US)
Pages (from-to)468-474
Number of pages7
JournalMolecular pharmacology
Volume95
Issue number5
DOIs
StatePublished - May 2019
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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