Intermediate filament (IF) proteins and heat shock proteins (HSPs) are large multi-membered families that share several features. These features include protein abundance, significant upregulation in response to a variety of stresses, function as cytoprotectors, and the phenocopying of several human diseases upon IF protein or HSP mutation. We are now coming to understand that these common elements point to IFs as important cellular stress proteins with some roles akin to those already well-characterized for HSPs. Unique functional roles for IFs include protection from mechanical stress while HSPs are characteristically involved in protein folding and as chaperones. Shared IF and HSP cytoprotective roles include inhibition of apoptosis, organelle homeostasis, and scaffolding. We review here recent data that corroborate the view that IFs function as highlyspecialized cytoskeletal stress proteins that promote cellular organization and homeostasis.
The stress responseTissues and cells are constantly subjected to stressful situations, meaning that components of the cell, including proteins, organelles and DNA, can be damaged. These stresses are both intrinsic, such as genetic and endoplasmic reticulum stress, and extrinsic/environmental stresses including heat, toxin or radiation, mechanical, wound and regenerative, infection, metabolic such as hypoxia and autophagy, osmotic and oxidative (Fig.1). The prototype response to stress, the heat stress response (HSR) is the best characterized and occurs via activation of heat shock transcription factors (HSFs), which drive the expression of multiple target genes containing the heat shock elements (HSEs) within their promoter sequence [1]. The heat shock proteins (HSPs) are the classical HSR targets and constitute a large family of proteins that are expressed constitutively and in response to stress [2] (Box 1). HSPs act as molecular chaperones assisting with normal folding, transport, and degradation of proteins and have an established stress-protective function, which extends far beyond the heat response [3,4] Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. The importance of keratins in stress-signal transmission may occur at focal adhesions since the viscoelastic response of keratin-null rat hepatoma cells is reduced, as compared with K8-or K18-containing cells, when measured using fibronectin-coated polystyrene beads and mechanical stress generated by optical tweezers [57]. Whether shear stress affects IF expression has not been studied in detail, although stretch induces K6 and decreases K10 expression [49,58]. Mechanic...
