General Structural and Functional Features of Molecular Chaperones

Edkins, Adrienne L.; Boshoff, Aileen

doi:10.1007/978-3-030-78397-6_2

Cited by 14 publications

(16 citation statements)

References 507 publications

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“…The main role of HSP40 is the regulation of HSP70 activity [ 21 ]. Additionally, Hsp40 facilitates the binding of Hsp70 to the Hsp90-Hop (heat shock organizing protein) complex for further control of the protein folding [ 22 , 23 , 24 ]. Taking into consideration the protective role of HSPs, the overexpression of chaperones was reported in various types of solid and hematological malignancies [ 25 , 26 , 27 , 28 , 29 ].…”

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

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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%

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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“…The major families of HSPs (HSP10, HSP40, HSP60, HSP70, HSP90, and HSP100) have now been shown to play essential roles in cell survival not only under stressful conditions but also under normal physiology, with many of them demonstrated to be molecular chaperones with both inducible and constitutive isoforms. 12 They are highly conserved from prokaryotes to eukaryotes, and in eukaryotes, they are found in all of the major subcellular compartments. The various chaperone families and associated regulatory cochaperones often work together to perform specific tasks.…”

Section: Malarial Hsps and Their Complexes As Drug Targetsmentioning

confidence: 99%

Plasmodium falciparum heat shock proteins as antimalarial drug targets: An update

Ahmad,

Alhammadi,

Almaazmi

et al. 2024

Cell Stress and Chaperones

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“…Low resolution structural studies suggest that PfHsp90 exists in solution as elongated and flexible dimers [ 37 ] ( Figure 2 ). While PfHsp90 shares significant sequence and structural similarity with its eukaryotic homologs, particularly cytosolic human Hsp90β (hHsp90), and contains all the characteristic domains (NTD, charged linker region, MD, CTD, and C-terminal dimerization domain ending in a MEEVD motif), it has several key structural and functional differences [ 45 , 46 , 47 ] ( Figure 2 ). In particular, the ATP-binding pocket of PfHsp90 is more hydrophobic, constricted, and basic, relative to hHsp90 [ 48 ].…”

Section: P Falciparum Hsp90smentioning

confidence: 99%

Hsp90 and Associated Co-Chaperones of the Malaria Parasite

et al. 2022

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Heat shock protein 90 (Hsp90) is one of the major guardians of cellular protein homeostasis, through its specialized molecular chaperone properties. While Hsp90 has been extensively studied in many prokaryotic and higher eukaryotic model organisms, its structural, functional, and biological properties in parasitic protozoans are less well defined. Hsp90 collaborates with a wide range of co-chaperones that fine-tune its protein folding pathway. Co-chaperones play many roles in the regulation of Hsp90, including selective targeting of client proteins, and the modulation of its ATPase activity, conformational changes, and post-translational modifications. Plasmodium falciparum is responsible for the most lethal form of human malaria. The survival of the malaria parasite inside the host and the vector depends on the action of molecular chaperones. The major cytosolic P. falciparum Hsp90 (PfHsp90) is known to play an essential role in the development of the parasite, particularly during the intra-erythrocytic stage in the human host. Although PfHsp90 shares significant sequence and structural similarity with human Hsp90, it has several major structural and functional differences. Furthermore, its co-chaperone network appears to be substantially different to that of the human host, with the potential absence of a key homolog. Indeed, PfHsp90 and its interface with co-chaperones represent potential drug targets for antimalarial drug discovery. In this review, we critically summarize the current understanding of the properties of Hsp90, and the associated co-chaperones of the malaria parasite.

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General Structural and Functional Features of Molecular Chaperones

Cited by 14 publications

References 507 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

Plasmodium falciparum heat shock proteins as antimalarial drug targets: An update

Hsp90 and Associated Co-Chaperones of the Malaria Parasite

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