Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Aug 2;3(3):e161.
doi: 10.1002/mco2.161. eCollection 2022 Sep.

Heat shock proteins: Biological functions, pathological roles, and therapeutic opportunities

Chen Hu  1   2 , Jing Yang  1   2 , Ziping Qi  1   2 , Hong Wu  1   2 , Beilei Wang  1   2 , Fengming Zou  1   2 , Husheng Mei  1   3 , Jing Liu  1   2   3 , Wenchao Wang  1   2   3 , Qingsong Liu  1   2   3   4
Affiliations
Review

Heat shock proteins: Biological functions, pathological roles, and therapeutic opportunities

Chen Hu et al. MedComm (2020). .

Abstract

The heat shock proteins (HSPs) are ubiquitous and conserved protein families in both prokaryotic and eukaryotic organisms, and they maintain cellular proteostasis and protect cells from stresses. HSP protein families are classified based on their molecular weights, mainly including large HSPs, HSP90, HSP70, HSP60, HSP40, and small HSPs. They function as molecular chaperons in cells and work as an integrated network, participating in the folding of newly synthesized polypeptides, refolding metastable proteins, protein complex assembly, dissociating protein aggregate dissociation, and the degradation of misfolded proteins. In addition to their chaperone functions, they also play important roles in cell signaling transduction, cell cycle, and apoptosis regulation. Therefore, malfunction of HSPs is related with many diseases, including cancers, neurodegeneration, and other diseases. In this review, we describe the current understandings about the molecular mechanisms of the major HSP families including HSP90/HSP70/HSP60/HSP110 and small HSPs, how the HSPs keep the protein proteostasis and response to stresses, and we also discuss their roles in diseases and the recent exploration of HSP related therapy and diagnosis to modulate diseases. These research advances offer new prospects of HSPs as potential targets for therapeutic intervention.

Keywords: cancers; heat shock proteins; molecular chaperone; proteostasis; target therapy.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

FIGURE 1
FIGURE 1
(A) Schematic diagram of the HSP70 domains. (B) The conformational cycles of HSP70. (C) Schematic diagram of the HSP90 domains. (D) The ATP‐dependent chaperone cycles of HSP90. (E) The structures of half football (PDB ID: 6MRD) and full football assembly (PDB ID: 6MRC) of HSP60‐HSP10, TRiC (PDB ID: 4A0O), images in Figure 1E adapted from Refs. 63 and 64. (F) The model of HSP60‐HSP10 chaperone cycles
FIGURE 2
FIGURE 2
The proteostasis network of heat shock proteins. The heat shock proteins participate in the folding of de novo synthesized peptides, also they hold the metastable proteins and folding intermediates, preventing them from aggregation. In addition, HSPs and their cochaperones also take charge of protein quality control and connect with protein degradation pathways
FIGURE 3
FIGURE 3
The HSP‐APC interaction modulates innate and adaptive immune responses
FIGURE 4
FIGURE 4
Immunomodulatory actions of HSPs in autoimmune diseases
See this image and copyright information in PMC

References

    1. Richter K, Haslbeck M, Buchner J. The heat shock response: life on the verge of death. Mol Cell. 2010;40(2):253‐266. - PubMed
    1. Ellis RJ. Protein misassembly: macromolecular crowding and molecular chaperones. Adv Exp Med Biol. 2007;594:1‐13. - PubMed
    1. Balch WE, Morimoto RI, Dillin A, Kelly JW. Adapting proteostasis for disease intervention. Science. 2008;319(5865):916‐919. - PubMed
    1. Hoter A, El‐Sabban ME, Naim HY. The HSP90 family: structure, regulation, function, and implications in health and disease. Int J Mol Sci. 2018;19(9):2560. - PMC - PubMed
    1. Hartl FU, Bracher A, Hayer‐Hartl M. Molecular chaperones in protein folding and proteostasis. Nature. 2011;475(7356):324‐332. - PubMed