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

Hu, Changwei; Yang, Jing; Zhou, Qi; Wu, Hong; Wang, Beilei; Zou, Fengming; Mei, Husheng; Liu, Jing; Wang, Qianqian; Liu, Qingsong

doi:10.1002/mco2.161

Cited by 189 publications

(140 citation statements)

References 435 publications

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“…Heat shock proteins constitute a family of conserved proteins in both prokaryotic and eukaryotic organisms that play an important role in the regulation of polypeptides and protein folding/unfolding (i.e., proteostasis), regulation of apoptosis and autophagy, and protection of cells from various stresses (including hypoxia, heat shock, ionizing radiation, etc.) ( Table 1 ) [ 10 , 11 , 12 ]. Therefore, the expression of HSPs is significantly increased in tumor cells as compared to normal cells [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…HSPs are classified according to their molecular weights constituting various families—HSPH (HSP110), HSPC (HSP90), HSPA (HSP70), DNAJ (HSP40), small HSP (HSPB), human chaperonin families CCT (TRiC), and HSPD/E ( Table 1 ) [ 14 ]. HSPs play a significant role in tumor cell proteostasis and evasion of apoptosis; they are involved in cancer cell division, DNA repair mechanisms, invasion, and metastasis [ 10 , 12 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Targeting Heat Shock Proteins in Malignant Brain Tumors: From Basic Research to Clinical Trials

Babi¹,

Menlibayeva²,

Bex³

et al. 2022

Cancers

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Heat shock proteins (HSPs) are conservative and ubiquitous proteins that are expressed both in prokaryotic and eukaryotic organisms and play an important role in cellular homeostasis, including the regulation of proteostasis, apoptosis, autophagy, maintenance of signal pathways, protection from various stresses (e.g., hypoxia, ionizing radiation, etc.). Therefore, HSPs are highly expressed in tumor cells, including malignant brain tumors, where they also associate with cancer cell invasion, metastasis, and resistance to radiochemotherapy. In the current review, we aimed to assess the diagnostic and prognostic values of HSPs expression in CNS malignancies as well as the novel treatment approaches to modulate the chaperone levels through the application of inhibitors (as monotherapy or in combination with other treatment modalities). Indeed, for several proteins (i.e., HSP10, HSPB1, DNAJC10, HSPA7, HSP90), a direct correlation between the protein level expression and poor overall survival prognosis for patients was demonstrated that provides a possibility to employ them as prognostic markers in neuro-oncology. Although small molecular inhibitors for HSPs, particularly for HSP27, HSP70, and HSP90 families, were studied in various solid and hematological malignancies demonstrating therapeutic potential, still their potential was not yet fully explored in CNS tumors. Some newly synthesized agents (e.g., HSP40/DNAJ inhibitors) have not yet been evaluated in GBM. Nevertheless, reported preclinical studies provide evidence and rationale for the application of HSPs inhibitors for targeting brain tumors.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Targeting Heat Shock Proteins in Malignant Brain Tumors: From Basic Research to Clinical Trials

Babi¹,

Menlibayeva²,

Bex³

et al. 2022

Cancers

View full text Add to dashboard Cite

show abstract

“…HSPs are involved in numerous biological processes related to protein stability, including protein folding, unfolding, synthesis, stabilization, and degradation, thus maintaining cellular homeostasis and protecting cells from endogenous and environmental stresses, such as hypoxia, infection, heat shock, chemicals, and radiation [ 3 , 4 ]. HSPs can also regulate normal cell physiology in immunologic processes, cell cycle regulation, transcriptional activation, and signal transduction [ 5 , 6 ]. In mammals, HSPs are classified into six families based on their relative molecular weights, including small HSPs, HSP40, HSP60, HSP70, HSP90, and HSP100 [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Multi-Faceted Roles of DNAJB Protein in Cancer Metastasis and Clinical Implications

Kim

2022

IJMS

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Heat shock proteins (HSPs) are highly conserved molecular chaperones with diverse cellular activities, including protein folding, assembly or disassembly of protein complexes, and maturation process under diverse stress conditions. HSPs also play essential roles in tumorigenesis, metastasis, and therapeutic resistance across cancers. Among them, HSP40s are widely accepted as regulators of HSP70/HSP90 chaperones and an accumulating number of biological functions as molecular chaperones dependent or independent of either of these chaperones. Despite large numbers of HSP40s, little is known about their physiologic roles, specifically in cancer progression. This article summarizes the multi-faceted role of DNAJB proteins as one subclass of the HSP40 family in cancer development and metastasis. Regulation and deregulation of DNAJB proteins at transcriptional, post-transcriptional, and post-translational levels contribute to tumor progression, particularly cancer metastasis. Furthermore, understanding differences in function and regulating mechanism between DNAJB proteins offers a new perspective on tumorigenesis and metastasis to improve therapeutic opportunities for malignant diseases.

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“…The heat shock proteins (Hsps), which not only facilitate protein folding, assembly, transportation, but also assist misfolded proteins to refold into functional states and degrade impaired proteins, are crucial in maintaining cellular homeostasis (Hu, Yang et al, 2022). Based on these salient characteristics, Hsps, including Hsp family, are often usurped by viruses to benefit their own survival (Zhang & Yu, 2022).…”

Section: Introductionmentioning

confidence: 99%

Chaperones Hsc70 and Hsp70 Play Distinct Roles in Bocaparvovirus Minute Virus of Canines Infection

Guo

Sun

Yan

et al. 2022

Preprint

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Minute virus of canines (MVC) belongs to the genus Bocaparvovirus and reproduces rapidly in its permissive cells Walter Reed/3873D (WRD). The crosstalk between MVC and WRD is poorly characterized in terms of molecular requirements and mechanisms. Here, we identified two novel cellular proteins Hsc70 and Hsp70 that interact with both NS1 and VP2 via mass spectrometry (MS), co-immunoprecipitation (Co-IP) and confocal immunofluorescence assays (IFA). Hsp70 was upregulated upon MVC infection. Respective silencing of Hsc70 and Hsp70 led to contrasting results at nearly every stage of MVC life cycle, including virus entry, transcription, translation, replication and production. Strikingly, transfection with low and high dose of pFlag-Hsp70 contributed to opposing impacts on viral protein levels and virus production possibly through a ubiquitin-dependent manner, indicating that MVC is quite sensitive to the levels of Hsp70. Treatment with quercetin and VER155008, two Hsp70 family inhibitors, both significantly decreased viral replication and particle levels. Together, these results illustrated that both Hsc70 and Hsp70 are involved in MVC life cycle, and targeting to Hsp70 family may represent a novel anti-MVC mechanism.

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

Cited by 189 publications

References 435 publications

Targeting Heat Shock Proteins in Malignant Brain Tumors: From Basic Research to Clinical Trials

Targeting Heat Shock Proteins in Malignant Brain Tumors: From Basic Research to Clinical Trials

Multi-Faceted Roles of DNAJB Protein in Cancer Metastasis and Clinical Implications

Chaperones Hsc70 and Hsp70 Play Distinct Roles in Bocaparvovirus Minute Virus of Canines Infection

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