scholarly journals C-terminal sequences of hsp70 and hsp90 as non-specific anchors for tetratricopeptide repeat (TPR) proteins

2009 ◽  
Vol 423 (3) ◽  
pp. 411-419 ◽  
Author(s):  
Andrew J. Ramsey ◽  
Lance C. Russell ◽  
Michael Chinkers
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Homo Sapiens ◽  
Heat Shock Protein 90 ◽  
Phage Library ◽  
Tetratricopeptide Repeat ◽  
Terminal Sequence ◽  
C Terminus ◽  
Multiple Copies ◽  
Shock Proteins

Steroid-hormone-receptor maturation is a multi-step process that involves several TPR (tetratricopeptide repeat) proteins that bind to the maturation complex via the C-termini of hsp70 (heat-shock protein 70) and hsp90 (heat-shock protein 90). We produced a random T7 peptide library to investigate the roles played by the C-termini of the two heat-shock proteins in the TPR–hsp interactions. Surprisingly, phages with the MEEVD sequence, found at the C-terminus of hsp90, were not recovered from our biopanning experiments. However, two groups of phages were isolated that bound relatively tightly to HsPP5 (Homo sapiens protein phosphatase 5) TPR. Multiple copies of phages with a C-terminal sequence of LFG were isolated. These phages bound specifically to the TPR domain of HsPP5, although mutation studies produced no evidence that they bound to the domain's hsp90-binding groove. However, the most abundant family obtained in the initial screen had an aspartate residue at the C-terminus. Two members of this family with a C-terminal sequence of VD appeared to bind with approximately the same affinity as the hsp90 C-12 control. A second generation pseudo-random phage library produced a large number of phages with an LD C-terminus. These sequences acted as hsp70 analogues and had relatively low affinities for hsp90-specific TPR domains. Unfortunately, we failed to identify residues near hsp90's C-terminus that impart binding specificity to individual hsp90–TPR interactions. The results suggest that the C-terminal sequences of hsp70 and hsp90 act primarily as non-specific anchors for TPR proteins.

C-terminal heat shock protein 90 modulators produce desirable oncogenic properties

2015 ◽  
Vol 13 (16) ◽  
pp. 4627-4631 ◽  
Author(s):  
Y. Wang ◽  
S. R. McAlpine
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Response ◽  
Heat Shock Protein 90 ◽  
Cellular Protection ◽  
Protection Mechanism ◽  
C Terminus ◽  
N Terminus ◽  
Shock Response

The cellular protection mechanism, the heat shock response, is only activated by classical heat shock 90 inhibitors (Hsp90) that “target” the N-terminus of the protein, but not by those that modulate the C-terminus.

Blocking the heat shock response and depleting HSF-1 levels through heat shock protein 90 (hsp90) inhibition: a significant advance on current hsp90 chemotherapies

RSC Advances ◽  
2015 ◽  
Vol 5 (73) ◽  
pp. 59003-59013 ◽  
Author(s):  
Yen Chin Koay ◽  
Jeanette R. McConnell ◽  
Yao Wang ◽  
Shelli R. McAlpine
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Response ◽  
Heat Shock Protein 90 ◽  
Significant Advance ◽  
Hsp90 Inhibition ◽  
C Terminus ◽  
Shock Response

C-terminal inhibitors of heat shock protein 90 (hsp90) modulate the C-terminus and do not elicit a heat shock response.

The first report of direct inhibitors that target the C-terminal MEEVD region on heat shock protein 90

2016 ◽  
Vol 52 (3) ◽  
pp. 501-504 ◽  
Author(s):  
L. K. Buckton ◽  
H. Wahyudi ◽  
S. R. McAlpine
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
First Report ◽  
C Terminus ◽  
Direct Inhibitors

Inhibitors binding to the C-terminus of Hsp90 and blocking access to the TPR co-chaperones.

scholarly journals Heat shock protein 90: its inhibition and function

2017 ◽  
Vol 373 (1738) ◽  
pp. 20160527 ◽  
Author(s):  
Abbey D. Zuehlke ◽  
Michael A. Moses ◽  
Len Neckers
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Bacterial Infections ◽  
Large Range ◽  
Heat Shock Protein 90 ◽  
Protein Maturation ◽  
Theme Issue ◽  
Shock Proteins ◽  
And Function ◽  
Dynamic Interplay

The molecular chaperone heat shock protein 90 (Hsp90) facilitates metastable protein maturation, stabilization of aggregation-prone proteins, quality control of misfolded proteins and assists in keeping proteins in activation-competent conformations. Proteins that rely on Hsp90 for function are delivered to Hsp90 utilizing a co-chaperone–assisted cycle. Co-chaperones play a role in client transfer to Hsp90, Hsp90 ATPase regulation and stabilization of various Hsp90 conformational states. Many of the proteins chaperoned by Hsp90 (Hsp90 clients) are essential for the progression of various diseases, including cancer, Alzheimer's disease and other neurodegenerative diseases, as well as viral and bacterial infections. Given the importance of these clients in different diseases and their dynamic interplay with the chaperone machinery, it has been suggested that targeting Hsp90 and its respective co-chaperones may be an effective method for combating a large range of illnesses. This article is part of the theme issue ‘Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective’.

Heat shock proteins and human pathogens

1995 ◽  
Vol 73 (S1) ◽  
pp. 1077-1080 ◽  
Author(s):  
J. P. Burnie
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Invasive Aspergillosis ◽  
Recombinant Antibody ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Heat Shock Protein 90 ◽  
Human Pathogens ◽  
Degree Of Protection ◽  
Shock Proteins ◽  
Mouse Model Of Infection

Recent years have seen the identification of heat shock protein 90 (HSP90) as one of sthe key immunodominant antigens in systemic fungal infection. In disseminated candidiasis, patients seroconvert when they recover from the infection. In a mouse model of infection, human, mouse, and human recombinant antibody all showed a degree of protection. HSP90 is also immunodominant in patients with an aspergilloma, allergic bronchopulmonary aspergillosis, and invasive aspergillosis who mount an antibody response. This paper argues the case for immunotherapy with antibody in treating these serious infections. Key words: heat shock protein 90, invasive candidiasis, invasive aspergillosis, immunotherapy.

scholarly journals Bronchial thermoplasty in asthma: an exploratory histopathological evaluation in distinct asthma endotypes/phenotypes

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Eleni Papakonstantinou ◽  
Triantafyllia Koletsa ◽  
Liang Zhou ◽  
Lei Fang ◽  
Michael Roth ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Heat Shock ◽  
Epithelial Cells ◽  
Heat Shock Proteins ◽  
Heat Shock Protein ◽  
Glucocorticoid Receptor ◽  
Airway Smooth Muscle ◽  
Heat Shock Protein 90 ◽  
Bronchial Thermoplasty ◽  
Shock Proteins

Abstract Background Bronchial thermoplasty regulates structural abnormalities involved in airway narrowing in asthma. In the present study we aimed to investigate the effect of bronchial thermoplasty on histopathological bronchial structures in distinct asthma endotypes/phenotypes. Methods Endobronchial biopsies (n = 450) were collected from 30 patients with severe uncontrolled asthma before bronchial thermoplasty and after 3 sequential bronchial thermoplasties. Patients were classified based on blood eosinophils, atopy, allergy and smoke exposure. Tissue sections were assessed for histopathological parameters and expression of heat-shock proteins and glucocorticoid receptor. Proliferating cells were determined by Ki67-staining. Results In all patients, bronchial thermoplasty improved asthma control (p < 0.001), reduced airway smooth muscle (p = 0.014) and increased proliferative (Ki67 +) epithelial cells (p = 0.014). After bronchial thermoplasty, airway smooth muscle decreased predominantly in patients with T2 high asthma endotype. Epithelial cell proliferation was increased after bronchial thermoplasty in patients with low blood eosinophils (p = 0.016), patients with no allergy (p = 0.028) and patients without smoke exposure (p = 0.034). In all patients, bronchial thermoplasty increased the expression of glucocorticoid receptor in epithelial cells (p = 0.018) and subepithelial mesenchymal cells (p = 0.033) and the translocation of glucocorticoid receptor in the nucleus (p = 0.036). Furthermore, bronchial thermoplasty increased the expression of heat shock protein-70 (p = 0.002) and heat shock protein-90 (p = 0.001) in epithelial cells and decreased the expression of heat shock protein-70 (p = 0.009) and heat shock protein-90 (p = 0.002) in subepithelial mesenchymal cells. The effect of bronchial thermoplasty on the expression of heat shock proteins -70 and -90 was distinctive across different asthma endotypes/phenotypes. Conclusions Bronchial thermoplasty leads to a diminishment of airway smooth muscle, to epithelial cell regeneration, increased expression and activation of glucocorticoid receptor in the airways and increased expression of heat shock proteins in the epithelium. Histopathological effects appear to be distinct in different endotypes/phenotypes indicating that the beneficial effects of bronchial thermoplasty are achieved by diverse molecular targets associated with asthma endotypes/phenotypes.

Heat-shock protein 70 and heat-shock protein 90 associate with Toll-like receptor 4 in response to bacterial lipopolysaccharide

2004 ◽  
Vol 32 (4) ◽  
pp. 636-639 ◽  
Author(s):  
M. Triantafilou ◽  
K. Triantafilou
Keyword(s):  
Heat Shock ◽  
Cell Surface ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
Innate Immune ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Surface Receptors ◽  
Innate Recognition ◽  
Shock Proteins

Mammalian responses to bacterial LPS (lipopolysaccharide) from the outer membrane of Gram-negative bacteria can lead to an uncontrolled inflammatory response that can be deadly for the host. It has been shown that the innate immune system employs at least three cell surface receptors, CD14, TLR4 (Toll-like receptor 4) and MD-2, in order to recognize bacterial LPS. In our previous work we have found that Hsps (heat-shock proteins) are also involved in the innate recognition of bacterial products. Their presence on the cell surface, as well as their involvement in the innate recognition process, are poorly understood. In the present study we have investigated the association of TLR4 with Hsp70 and Hsp90 following LPS stimulation, both on the cell surface and intracellularly. Our results show that Hsp70 and Hsp90 form a cluster with TLR4 within lipid microdomains following LPS stimulation. In addition, Hsp70 and Hsp90 seem to be involved in TLR4/LPS trafficking and targeting to the Golgi apparatus, since upon LPS stimulation we found that both Hsps are targeted to the Golgi along with TLR4. The present study sheds new light into the involvement of Hsps in the innate immune response.

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