Abstract
Heat shock proteins (Hsp) are a diverse group of constitutive and/or stress-induced molecules that are categorized into several classes on the basis of their molecular weight. Mammalian Hsp have been mostly regarded as intracellular chaperones that mediate a range of essential cellular functions, including proper folding of newly synthesized polypeptides, refolding of denatured proteins, protein transport, and stabilization of native proteins’ structures. The well-characterized and highly evolutionarily conserved, stress-inducible 70-kDa heat shock protein (Hsp70), is a key molecular chaperone that is overexpressed in the cell in response to stress of various origin. Hsp70 exhibits an immunosuppressive activity via, e.g., downregulation of the nuclear factor-kappa B (NF-κB) activation, and pharmacological induction of Hsp70 can ameliorate the autoimmune arthritis development in animal models. Moreover, Hsp70 might be passively or actively released from the necrotic or stressed cells, respectively. Highly immunogenic extracellular Hsp70 has been reported to impact both the innate and adaptive immune responses, and to be implicated in the autoimmune reaction. In addition, preclinical studies revealed that immunization with highly conserved Hsp70 peptides could be regarded as a potential treatment target for autoimmune arthritis, such as the rheumatoid arthritis, via induction of antigen-specific regulatory T helper cells (also called Treg). Here, a dual role of the intra- and extracellular Hsp70 is presented in the context of the autoimmune reaction.
Highlights
Heat shock proteins (Hsp) are a group of constitutive and/or stress-induced molecular chaperones that are categorized into several classes, including Hsp110, Hsp90, Hsp70, Hsp60, Hsp40, and the so-called small Hsp [1]
The above-mentioned conflicting results suggest that Hsp70 may play a dual role in the extracellular space that may depend on the type of cells which interact with such chaperones and the type of the disease
The Hsp70 family of molecular chaperones displays various biological functions both, inside and outside the cell. Their intracellular roles do involve folding or transport of polypeptides, but they act as important cell signaling molecules involved in either control of the immune responses or promotion of cancer development
Summary
Heat shock proteins (Hsp) are a group of constitutive and/or stress-induced molecular chaperones that are categorized into several classes, including Hsp110, Hsp, Hsp, Hsp, Hsp, and the so-called small Hsp (sHsps) [1]. The well-characterized and highly evolutionarily conserved stress-inducible 70-kDa heat shock protein (Hsp70) is a key molecular chaperone that is overexpressed in the cell under stress conditions. Hsp preferentially binds hydrophobic regions of newly synthesized linear peptides or exposed regions of partially unfolded proteins It seems that such interactions lack strong sequence specificity and allow Hsp to bind to a variety of “client proteins”, including cell signaling molecules. For these chaperones, ATP hydrolysis results from binding of substrates to the SBD domain with concomitant NBD interactions with the.
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