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.

N-terminal and C-terminal modulation of Hsp90 produce dissimilar phenotypes

2015 ◽  
Vol 51 (8) ◽  
pp. 1410-1413 ◽  
Author(s):  
Y. Wang ◽  
S. R. McAlpine
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Cancer Cells ◽  
Heat Shock Response ◽  
Heat Shock Protein 90 ◽  
Hsp90 Inhibitors ◽  
Survival Mechanism ◽  
N Terminus ◽  
Shock Response

Classic oncogenic heat shock protein 90 (Hsp90) inhibitors target the N-terminus of the protein, triggering a survival mechanism in cancer cells referred to as the heat shock response (HSR).

Induction of the heat shock response in Arabidopsis by heat shock protein 70 inhibitor VER-155008

2019 ◽  
Vol 46 (10) ◽  
pp. 925
Author(s):  
Erina Matsuoka ◽  
Naoki Kato ◽  
Masakazu Hara
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Response ◽  
Wheat Germ ◽  
Heat Shock Protein 90 ◽  
Hsp90 Inhibitor ◽  
Wheat Germ Extract ◽  
Chlorophyll Contents ◽  
Shock Response ◽  
Human Hsp70

The heat shock protein 90 (HSP90) inhibitor, geldanamycin, is a chemical inducer of the heat shock response (HSR) in Arabidopsis. Geldanamycin is thought to activate the heat shock signal by dissociating the HSP90-heat shock factor (HSF) complex. Recent studies have indicated that plant HSP70 is also associated with HSF, suggesting that inhibition of HSP70 may induce the HSR. However, no studies have been conducted to test this hypothesis. Here, we found that a specific HSP70 inhibitor VER-155008 activated the promoter of a small HSP gene (At1 g53540, HSP17.6C-CI) of Arabidopsis, which was shown to be activated by geldanamycin and other HSP90 inhibitors. The production of HSP17.6C-CI, HSP70 and HSP90.1 proteins in Arabidopsis was enhanced by the addition of VER-155008. The reduction of chlorophyll contents by heat shock was ameliorated by VER-155008. Chaperone analyses indicated that VER-155008 inhibited the chaperone activities of wheat germ extract and human HSP70/HSP40, respectively. These results suggest that the inhibition of HSP70 by VER-155008 enhanced the heat tolerance of Arabidopsis by inducing the HSR in the plant.

scholarly journals Molecular cloning, phylogenetic analysis and heat shock response of Babesia gibsoni heat shock protein 90

2016 ◽  
Vol 78 (8) ◽  
pp. 1355-1360 ◽  
Author(s):  
Masahiro YAMASAKI ◽  
Yoshihiro TSUBOI ◽  
Yusuke TANIYAMA ◽  
Naohiro UCHIDA ◽  
Reeko SATO ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Molecular Cloning ◽  
Heat Shock Response ◽  
Heat Shock Protein 90 ◽  
Babesia Gibsoni ◽  
Shock Response

A purine-type heat shock protein 90 inhibitor promotes the heat shock response in Arabidopsis

2017 ◽  
Vol 11 (2) ◽  
pp. 107-113 ◽  
Author(s):  
Hiroki Murano ◽  
Takumi Matsubara ◽  
Ikuo Takahashi ◽  
Masakazu Hara
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Response ◽  
Heat Shock Protein 90 ◽  
Shock Response

scholarly journals C-terminal HSP90 Inhibitors Block the HSP90:HIF-1α Interaction and Inhibit the Cellular Hypoxic Response

2019 ◽  
Author(s):  
Nalin Kataria ◽  
Bernadette Kerr ◽  
Samantha S. Zaiter ◽  
Shelli McAlpine ◽  
Kristina M Cook
Keyword(s):  
Heat Shock ◽  
Heat Shock Response ◽  
Hypoxia Inducible Factor ◽  
Chemotherapy Resistance ◽  
Heat Shock Protein 90 ◽  
Low Oxygen ◽  
Hsp90 Inhibitors ◽  
Hypoxic Response ◽  
C Terminus ◽  
Shock Response

Hypoxia Inducible Factor (HIF) is a transcription factor activated by low oxygen, which is common in solid tumours. HIF controls the expression of genes involved in angiogenesis, chemotherapy resistance and metastasis. The chaperone HSP90 (Heat Shock Protein 90) stabilizes the subunit HIF-1α and prevents degradation. Previously identified HSP90 inhibitors bind to the N-terminal pocket of HSP90 which blocks binding to HIF-1α, and produces HIF-1α degradation. N-terminal inhibitors have failed in the clinic as single therapy treatments due in part because they induce a heat shock response, which increases chemotherapy resistance. SM molecules are HSP90 inhibitors that bind to the C-terminus and do not activate the heat shock response. The effects of C-terminal HSP90 inhibitors on HIF-1α are unreported. Herein we show that SM compounds block binding between HSP90 and HIF-1α, leading to HIF-1α degradation through the proteasome using the PHD/pVHL pathway in hypoxic conditions. The SM compounds decrease HIF-1α target gene expression at the mRNA and protein level under hypoxia in colorectal cancer cells, leading to cell death, without inducing a heat shock response. Our results suggest that targeting the C-terminus of HSP90 blocks the hypoxic response and may be an effective anti-cancer strategy.

scholarly journals X66, a novel N-terminal heat shock protein 90 inhibitor, exerts antitumor effects without induction of heat shock response

Oncotarget ◽  
2016 ◽  
Vol 7 (20) ◽  
pp. 29648-29663 ◽  
Author(s):  
Zhixin Zhao ◽  
Jianming Zhu ◽  
Haitian Quan ◽  
Guimin Wang ◽  
Bo Li ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Response ◽  
Heat Shock Protein 90 ◽  
Antitumor Effects ◽  
Shock Response

scholarly journals Heat Shock Protein 90 Homeostasis Controls Stage Differentiation in Leishmania donovani

2001 ◽  
Vol 12 (11) ◽  
pp. 3307-3316 ◽  
Author(s):  
Martina Wiesgigl ◽  
Joachim Clos
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Response ◽  
Leishmania Donovani ◽  
Morphological Differentiation ◽  
Heat Shock Protein 90 ◽  
Shock Response ◽  
Feedback Inhibitor ◽  
Hsp 90 ◽  
Leishmania Parasites

The differentiation of Leishmania parasites from the insect stage, the promastigote, toward the pathogenic mammalian stage, the amastigote, is triggered primarily by the rise in ambient temperature encountered during the insect-to-mammal transmission. We show here that inactivation of heat shock protein (Hsp) 90, with the use of the drugs geldanamycin or radicicol, mimics transmission and induces the differentiation from the promastigote to the amastigote stage. Geldanamycin also induces a growth arrest of cultured promastigotes that can be forestalled by overexpression of the cytoplasmic Hsp90. Moreover, we demonstrate that Hsp90 serves as a feedback inhibitor of the cellular heat shock response inLeishmania. Our results are consistent with Hsp90 homeostasis serving as cellular thermometer for these primitive eukaryotes, controlling both the heat shock response and morphological differentiation.

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