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HSP90 binds KCNH2. 42 / 43
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"Moreover, enhancement of the HERG:HSP90 interaction is responsible for the increased membrane trafficking induced by estradiol xref ."
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"Similarly the antibiotic geldanamycin inhibits the formation of the hERG–Hsp90 complex that accelerates hERG channel degradation [114] ."
25770776
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"Increased ROS level interferes in the association of hERG with Hsp90 (Heat Shock Protein 90) and causes retention of the channel in endoplasmic reticulum [ xref ]."
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"A specific inhibitor of Hsp90, the antibiotic geldanamycin ( Whitesell et al., 1994 ) accelerates hERG channel degradation by inhibiting the formation of hERG–Hsp90 complexes by blockade of the functi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24998878
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"Similarly, Hsp90 inhibitors are generally hypothesized to have a risk of TdP, via accelerating hERG channel degradation by inhibiting hERG-Hsp90 complex formation ( Dennis et al., 2007; Ficker et al.,[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30391349
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"It could be that hypoxia inhibits Hsp90 binding to hERG by reducing steady state expression levels of endogenous Hsp90 and/or Hsp70."
19654002
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"To further confirm the role of ROS in Hsp90 binding to hERG, normoxic cells were exposed to xanthine and xanthine oxidase (X/XO; 500microm/5milliunits/ml), which generates O 2 -."
19654002
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"For hERG protein trafficking, a study showed that the reduced expression level of hERG protein is linked with impaired trafficking because of the diminished interaction between hERG and HSP90 (Figure 3G) (197)."
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"The modulation of Hsp90 interaction with hERG during hypoxia is mediated by ROS generated during prolonged hypoxic exposure."
19654002
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"The complete absence of Hsp90 binding to hERG during hypoxia observed in our studies is in contrast to what is observed with trafficking deficient LQT2 mutants (hERG R752W and G601S), in which the interactions of Hsp90 and Hsp70 are increased for both mutants [XREF_BIBR]."
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"Two mechanisms could account for how ROS regulates hERG protein interaction with Hsp90."
19654002
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"Hsp70 interacts with the nascent hERG in the ER while Hsp90 interacts with the terminal hERG in the cytoplasm to facilitate folding [ xref ]."
28763460
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"The interaction between hERG protein and Hsp90 reduced while the interaction between hERG protein and Hsp70 increased by DHB."
28763460
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"Hsp90 was downregulated by DHB, which may have directly decreased the interaction between the terminal hERG protein and Hsp90 and resulted in an accumulation of a large quantity of hERG protein that folded incorrectly."
28763460
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"This was supported by demonstration of a unique and specific KCNH2 interaction with Hsp90 over several other K channels lacking these domains."
19959132
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"Therefore, it would be difficult for Hsp70 to recognize and interact with the hERG protein, thereby elongating the interaction of the early hERG protein with Hsp70 and reducing the interaction of hERG protein with Hsp90."
28763460
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"Geldanamycin was the first compound shown to inhibit hERG trafficking, and it does so by interfering with the association of the chaperone Hsp90 with hERG in the ER ( Ficker et al., 2003 )."
15950494
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"A specific inhibitor of Hsp90, the antibiotic geldanamycin ( Whitesell et al., 1994 ) accelerates hERG channel degradation by inhibiting the formation of hERG–Hsp90 complexes by blockade of the functi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24998878
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"Hsp70 interacts with the nascent hERG in the ER while Hsp90 interacts with the terminal hERG in the cytoplasm to facilitate folding [XREF_BIBR]."
28763460
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"Both HSP70 and HSP90 directly interact with hERG (the human ether-a-go-go-related gene) whose disorders can lead to long-QT syndrome and sudden cardiac death [XREF_BIBR]."
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"Geldanamycin accelerates the degradation of immature hERG channels by inhibiting the protective formation of immature hERG and Hsp90 complexes and promoting channel ubiquitination ( Ficker et al., 200[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30391349
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"Immunoprecipitation with anti-Hsp90 showed that Hsp90 interacted with hERG in cells co-transfected with hERG and Kv4.3."
29259226
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"For hERG protein trafficking, a study showed that the reduced expression level of hERG protein is linked with impaired trafficking because of the diminished interaction between hERG and HSP90 ( xref ) ( xref )."
38420267
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"We therefore investigated whether ROS, by modulating the interaction of hERG with Hsp90, mediates hypoxia-induced hERG downregulation."
19654002
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"Prolonged association of hERG with molecular chaperone Hsp90 resulting in complex oligomeric insoluble aggregates contributed to ER accumulation and trafficking defect."
31017964
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"To further confirm the role of ROS in Hsp90 binding to hERG, normoxic cells were exposed to xanthine/xanthine oxidase (X/XO; 500µm/5milliunits/ml), which generates O 2 − ."
19654002
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"However, Hsp90 preferably interacted with hERG in cells co-transfected with hERG and Kv4.3 and enhanced the expression of 135kDa hERG."
29259226
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"The modulation of Hsp90 interaction with hERG during hypoxia is mediated by ROS generated during prolonged hypoxic exposure."
19654002
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"Our pulse chase studies show that hypoxia inhibits progression of the cg form into the fg form of hERG due to a direct consequence of the interference of Hsp90 binding to nascent hERG molecules."
19654002
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"The complete absence of Hsp90 binding to hERG during hypoxia observed in our studies is in contrast to what is observed with trafficking-deficient LQT2 mutants (hERG R752W and G601S), in which the interactions of Hsp90 and Hsp70 are increased for both mutants [ xref ]."
19654002
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"Using biochemical and electrophysiological assays we show that the cytosolic chaperones Hsp70 and Hsp90 interact transiently with wild-type hERG."
16050262
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"The decrease in translation may be an important adaptive response of cells, triggered by the hERG protein that cannot bind to Hsp90 and fold successfully."
19654002
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"Our finding that ROS scavengers restore hERG interaction with Hsp90 could account for the stabilization of hERG protein by antioxidants during hypoxia."
19654002
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"Two mechanisms could account for how ROS regulates hERG protein interaction with Hsp90."
19654002
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"Modulation of hERG interaction with Hsp90 by ROS leads to hERG trafficking defect by CH."
31017964
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"Similarly, Hsp90 inhibitors are generally hypothesized to have a risk of TdP, via accelerating hERG channel degradation by inhibiting hERG-Hsp90 complex formation ( Dennis et al., 2007; Ficker et al.,[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30391349
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"Geldanamycin accelerates the degradation of immature hERG channels by inhibiting the protective formation of immature hERG and Hsp90 complexes and promoting channel ubiquitination ( Ficker et al., 200[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30391349
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"Previous studies have shown that blocking Hsp90 binding to hERG by geldanamycin resulted in decreased surface expression of 150kDa form."
31017964
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"To further confirm that CH altered hERG interaction with Hsp90, we performed co-immunoprecipitation experiments."
31017964
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"Similar results were obtained when hERG-Hsp90 complexes were immunoprecipitated with Hsp90 antibody ( xref )."
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"There is evidence that reduced temperature culture can modulate the affinity between hERG and HSP 70 or HSP 90, which represents a possible explanation for the temperature dependence of folding and forward trafficking of hERG (35)."
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"To determine the mechanism of trafficking inhibition, we performed western blot and immunoprecipitation to test folding of hERG by assessing interaction between hERG and Hsp90 and Hsp70."
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