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  • Print publication year: 2005
  • Online publication date: August 2009

8 - Regulation of Signal Transduction by Intracellular and Extracellular Hsp70



There is a clear dichotomy between the effects of the 70-kDa heat shock protein (Hsp70) when expressed intracellularly and when released into the extracellular space. Intracellular Hsp70 is primarily implicated as a protein chaperone that transports and folds naïve, aberrantly folded, or mutated proteins, resulting in cytoprotection when cells are exposed to stressful stimuli – most notably heat shock itself. Intracellular Hsp70 also functions as a regulatory molecule and has a largely inhibitory function in cellular metabolism. In contrast, Hsp70 is implicated in immune activation, given that exposure of immunocompetent cells to exogenous Hsp70 triggers acute inflammatory responses, activates innate immunity and enhances anti-tumour surveillance. This review focuses on recent advances in understanding the contrasting roles of Hsp70 as an intracellular molecular chaperone and extracellular signalling ligand and highlights its relevance to host defence against pathogens and malignant transformation.

The formative studies of Hsp70, dating back over 30 years, suggested a strictly intracellular function for Hsp70 with the properties of a molecular chaperone – a protein that modulates the tertiary structures of other proteins and protects cells from stress [1, 2]. However, in 1989 Hightower and colleagues showed that cells in culture contain a pool of Hsp70 which is loosely associated with the cell and which could be released into the extracellular medium after heat shock or even after mild washing with tissue culture medium [3].

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