scholarly journals Membrane-Associated Heat Shock Proteins in Oncology: From Basic Research to New Theranostic Targets

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1263 ◽  
Author(s):  
Maxim Shevtsov ◽  
Zsolt Balogi ◽  
William Khachatryan ◽  
Huile Gao ◽  
László Vígh ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Molecular Chaperones ◽  
Intracellular Localization ◽  
Large Family ◽  
Basic Research ◽  
Stress Factors ◽  
Small Hsps ◽  
Stress Oxidative ◽  
Shock Proteins

Heat shock proteins (HSPs) constitute a large family of conserved proteins acting as molecular chaperones that play a key role in intracellular protein homeostasis, regulation of apoptosis, and protection from various stress factors (including hypoxia, thermal stress, oxidative stress). Apart from their intracellular localization, members of different HSP families such as small HSPs, HSP40, HSP60, HSP70 and HSP90 have been found to be localized on the plasma membrane of malignantly transformed cells. In the current article, the role of membrane-associated molecular chaperones in normal and tumor cells is comprehensively reviewed with implications of these proteins as plausible targets for cancer therapy and diagnostics.

Cellular Functions of Small Heat Shock Proteins (HSPB) in Hepatocellular Carcinoma

2021 ◽  
Vol 21 ◽  
Author(s):  
Noriko Yamada ◽  
Rie Matsushima-Nishiwaki ◽  
Kaido Kobayashi ◽  
Shota Takahata ◽  
Hidenori Toyoda ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Molecular Chaperones ◽  
Low Molecular Weight ◽  
Post Translational Modification ◽  
Cellular Functions ◽  
The Family ◽  
Small Hsps ◽  
Shock Proteins

Abstract: Heat shock proteins (HSPs) play an essential role as molecular chaperones in proteostasis. Small HSPs are a group of low-molecular-weight HSPs in the range of 12-43 kDa and are classified as HSPB. Within the ten members of the family, HSPB1 (HSP27), HSPB5 (B-crystallin), HSPB6 (HSP20), and HSPB8 (HSP22) ubiquitously exist in various tissues, including liver tissue. These small HSPs undergo phosphorylation as a post-translational modification, and their functions are modulated. Hepatocellular carcinoma (HCC) is one of the most frequent cancers and the fourth leading cause of cancer-related death worldwide. HSPs play a cytoprotective role as molecular chaperones. Thus, HSPB has been generally considered to protect HCC cells and help the progression of HCC. On the other hand, recent studies from our laboratories have demonstrated suppressive roles of phospho-HSPB1, HSPB6, and HSPB8 in progression of HCC. These findings may provide a basis for a novel defense system by HSPB against HCC progression. This review focuses on the cellular functions of HSPB in HCC and summarizes the current research.

Principles of chaperone-mediated protein folding

1995 ◽  
Vol 348 (1323) ◽  
pp. 107-112 ◽  
Keyword(s):  
Protein Folding ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Molecular Chaperones ◽  
Cellular Protein ◽  
Chaperone Proteins ◽  
Shock Proteins ◽  
Polypeptide Chains

The recent discovery of molecular chaperones and their functions has changed dramatically our view of the processes underlying the folding of proteins in vivo . Rather than folding spontaneously, most newly synthesized polypeptide chains seem to acquire their native conformations in a reaction mediated by chaperone proteins. Different classes of molecular chaperones, such as the members of the Hsp70 and Hsp60 families of heat-shock proteins, cooperate in a coordinated pathway of cellular protein folding.

Heat shock proteins: Molecular chaperones

1991 ◽  
Vol 19 (4) ◽  
pp. 166-172 ◽  
Author(s):  
Najma Ali ◽  
Naheed Banu
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Molecular Chaperones ◽  
Shock Proteins

scholarly journals Developmental Expression and Functions of the Small Heat Shock Proteins in Drosophila

2018 ◽  
Vol 19 (11) ◽  
pp. 3441 ◽  
Author(s):  
Teresa Jagla ◽  
Magda Dubińska-Magiera ◽  
Preethi Poovathumkadavil ◽  
Małgorzata Daczewska ◽  
Krzysztof Jagla
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Large Family ◽  
Active Role ◽  
Stress Conditions ◽  
Developmental Expression ◽  
Shsp Gene ◽  
Time Specific ◽  
Shock Proteins ◽  
And Function

Heat shock proteins (Hsps) form a large family of evolutionarily conserved molecular chaperones that help balance protein folding and protect cells from various stress conditions. However, there is growing evidence that Hsps may also play an active role in developmental processes. Here, we take the example of developmental expression and function of one class of Hsps characterized by low molecular weight, the small Hsps (sHsps). We discuss recent reports and genome-wide datasets that support vital sHsps functions in the developing nervous system, reproductive system, and muscles. This tissue- and time-specific sHsp expression is developmentally regulated, so that the enhancer sequence of an sHsp gene expressed in developing muscle, in addition to stress-inducible elements, also carries binding sites for myogenic regulatory factors. One possible reason for sHsp genes to switch on during development and in non-stress conditions is to protect vital developing organs from environmental insults.

scholarly journals Molecular chaperones and heat shock proteins in atherosclerosis

2012 ◽  
Vol 302 (3) ◽  
pp. H506-H514 ◽  
Author(s):  
Qingbo Xu ◽  
Bernhard Metzler ◽  
Marjan Jahangiri ◽  
Kaushik Mandal
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Molecular Chaperones ◽  
Mammalian Cells ◽  
Vessel Wall ◽  
Protective Role ◽  
Research Field ◽  
Stressed Cells ◽  
Shock Proteins ◽  
Prevention Of Atherosclerosis

In response to stress stimuli, mammalian cells activate an ancient signaling pathway leading to the transient expression of heat shock proteins (HSPs). HSPs are a family of proteins serving as molecular chaperones that prevent the formation of nonspecific protein aggregates and assist proteins in the acquisition of their native structures. Physiologically, HSPs play a protective role in the homeostasis of the vessel wall but have an impact on immunoinflammatory processes in pathological conditions involved in the development of atherosclerosis. For instance, some members of HSPs have been shown to have immunoregulatory properties and modification of innate and adaptive response to HSPs, and can protect the vessel wall from the disease. On the other hand, a high degree of sequence homology between microbial and mammalian HSPs, due to evolutionary conservation, carries a risk of misdirected autoimmunity against HSPs expressed on the stressed cells of vascular endothelium. Furthermore, HSPs and anti-HSP antibodies have been shown to elicit production of proinflammatory cytokines. Potential therapeutic use of HSP in prevention of atherosclerosis involves achieving optimal balance between protective and immunogenic effects of HSPs and in the progress of research on vaccination. In this review, we update the progress of studies on HSPs and the integrity of the vessel wall, discuss the mechanism by which HSPs exert their role in the disease development, and highlight the potential clinic translation in the research field.

scholarly journals Heat Shock Proteins in Alzheimer’s Disease: Role and Targeting

2018 ◽  
Vol 19 (9) ◽  
pp. 2603 ◽  
Author(s):  
Claudia Campanella ◽  
Andrea Pace ◽  
Celeste Caruso Bavisotto ◽  
Paola Marzullo ◽  
Antonella Marino Gammazza ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Molecular Chaperones ◽  
Protein Misfolding ◽  
Point Of View ◽  
Toxic Species ◽  
Shock Proteins

Among diseases whose cure is still far from being discovered, Alzheimer’s disease (AD) has been recognized as a crucial medical and social problem. A major issue in AD research is represented by the complexity of involved biochemical pathways, including the nature of protein misfolding, which results in the production of toxic species. Considering the involvement of (mis)folding processes in AD aetiology, targeting molecular chaperones represents a promising therapeutic perspective. This review analyses the connection between AD and molecular chaperones, with particular attention toward the most important heat shock proteins (HSPs) as representative components of the human chaperome: Hsp60, Hsp70 and Hsp90. The role of these proteins in AD is highlighted from a biological point of view. Pharmacological targeting of such HSPs with inhibitors or regulators is also discussed.

scholarly journals Small Molecule Inhibitors Targeting the Heat Shock Protein System of Human Obligate Protozoan Parasites

2019 ◽  
Vol 20 (23) ◽  
pp. 5930 ◽  
Author(s):  
Zininga ◽  
Shonhai
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Heat Shock Protein ◽  
Small Molecule ◽  
Molecular Chaperones ◽  
Small Molecule Inhibitors ◽  
Protozoan Parasites ◽  
Obligate Intracellular ◽  
Human Host ◽  
Shock Proteins

Obligate protozoan parasites of the kinetoplastids and apicomplexa infect human cells to complete their life cycles. Some of the members of these groups of parasites develop in at least two systems, the human host and the insect vector. Survival under the varied physiological conditions associated with the human host and in the arthropod vectors requires the parasites to modulate their metabolic complement in order to meet the prevailing conditions. One of the key features of these parasites essential for their survival and host infectivity is timely expression of various proteins. Even more importantly is the need to keep their proteome functional by maintaining its functional capabilities in the wake of physiological changes and host immune responses. For this reason, molecular chaperones (also called heat shock proteins)—whose role is to facilitate proteostasis—play an important role in the survival of these parasites. Heat shock protein 90 (Hsp90) and Hsp70 are prominent molecular chaperones that are generally induced in response to physiological stress. Both Hsp90 and Hsp70 members are functionally regulated by nucleotides. In addition, Hsp70 and Hsp90 cooperate to facilitate folding of some key proteins implicated in cellular development. In addition, Hsp90 and Hsp70 individually interact with other accessory proteins (co-chaperones) that regulate their functions. The dependency of these proteins on nucleotide for their chaperone function presents an Achille’s heel, as inhibitors that mimic ATP are amongst potential therapeutic agents targeting their function in obligate intracellular human parasites. Most of the promising small molecule inhibitors of parasitic heat shock proteins are either antibiotics or anticancer agents, whose repurposing against parasitic infections holds prospects. Both cancer cells and obligate human parasites depend upon a robust protein quality control system to ensure their survival, and hence, both employ a competent heat shock machinery to this end. Furthermore, some inhibitors that target chaperone and co-chaperone networks also offer promising prospects as antiparasitic agents. The current review highlights the progress made so far in design and application of small molecule inhibitors against obligate intracellular human parasites of the kinetoplastida and apicomplexan kingdoms.

scholarly journals Heat shock proteins: A review of the molecular chaperones

1999 ◽  
Vol 29 (4) ◽  
pp. 748-751 ◽  
Author(s):  
David Whitley ◽  
Steven P. Goldberg ◽  
William D. Jordan
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Molecular Chaperones ◽  
Shock Proteins
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