IndraLab

Statements

OTUD3 binds HSPA5. 38 / 38
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"Mechanistically, Rolapitant directly targeted the OTUD3-GRP78 axis to trigger endoplasmic reticulum (ER) stress-C/EBP homologous protein (CHOP)-DR5 signaling, sensitizing lung cancer cells to TRAIL-induced apoptosis."
38539203
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"In summary, the present study identifies Rolapitant as a novel inhibitor of deubiquitinase OTUD3 and establishes that the OTUD3-GRP78 axis is a potential therapeutic target for lung cancer."
38539203
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"Given that OTUDin3 binds to the OTU domain, we further investigated whether OTUDin3 disrupted the interaction between OTUD3 and GRP78 by performing co-IP and GST-pulldown assays."
37369659
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"Co-IP and GST-pulldown assays confirmed that OTUDin3 did not affect the interaction between OTUD3 and GRP78 (Fig. xref , Supplementary Fig. xref )."
37369659
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"In addition, a study on CHIP, an E3 ubiquitin ligase for OTUD3, further confirmed that OTUD3 promoted NSCLC through an OTUD3-GRP78 signaling axis [ xref ]."
37369659
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"In our present study, we identified Rolapitant as an inhibitor of OTUD3 that can also promote ER stress DR5-induced apoptosis of lung cancer cells through disrupting the interaction of OTUD3 with GRP78."
38539203
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"Besides, rolapitant may trigger the ER stress-CHOP-DR5 signaling pathway by targeting the OTUD3-GRP78 axis, enhancing TRAIL induced apoptosis in lung cancer cells ( xref )."
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"OTUD3 interacts with the glucose-regulated protein GRP78 to deubiquitinate and stabilize GRP78, thereby inhibiting lung cancer cell growth and migration ( xref )."
37829187
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"Given that OTUDin3 binds to the OTU domain, we further investigated whether OTUDin3 disrupted the interaction between OTUD3 and GRP78 by performing co-IP and GST-pulldown assays."
37369659
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"Co-IP and GST-pulldown assays confirmed that OTUDin3 did not affect the interaction between OTUD3 and GRP78 (Fig. 4F, Supplementary Fig. 4A)."
37369659
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"The ubiquitin ligase CHIP ubiquitinates OTUD3 to degrade it, and inhibition of the OTUD3-GRP78 signaling axis reduces tumor metastasis in lung cancer ( xref )."
37829187
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"OTUD3 interacts with GRP78."
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"Rolapitant directly targets the OTUD3-GRP78 axis to trigger ER stress-related CHOP-DR5 signaling, sensitizing lung cancer cells to TRAIL-induced apoptosis."
38539203
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"Moreover, purified GST-OTUD3 protein, but not the GST alone, was able to interact with His-GRP78 under cell-free conditions (Fig.  xref ), suggesting a direct interaction between GRP78 and OTUD3."
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"Based on these findings, we concluded that OTUDin3 inhibits NSCLC by targeting the OTUD3-GRP78 signaling axis (Fig. xref )."
37369659
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"Whereafter, the interaction between endogenous OTUD3 and GRP78 was detected in A549 and H1299 cells (Fig.  xref )."
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"Since OTUD3 is a classical member of the OTU family of the deubiquitylase, we wondered whether OTUD3 specifically interacted with GRP78."
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"Another DUB, OTUD3, regulates the carboxyl terminus of Hsc70-interacting protein (CHIP), which influences lung cancer metastasis by suppressing the OTUD3-GRP78 signal axis [ xref ]."
35884607
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"Given that Rolapitant binds to the OTU domain, we further investigated whether Rolapitant disrupted the interaction between OTUD3 and GRP78 by performing co-IP and GST pull-down assays."
38539203
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"Co-IP and GST pull-down assays confirmed that Rolapitant did not affect the interaction between OTUD3 and GRP78 (Fig. xref F, H)."
38539203
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"Rolapitant upregulates CHOP by triggering ER stress through modulating the OTUD3-GRP78 axis in lung cancer cells."
38539203
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"Based on this finding, we investigated whether Rolapitant can trigger ER stress-induced apoptosis through the OTUD3-GRP78 axis."
38539203
reach
"Given that Rolapitant binds to the OTU domain, we further investigated whether Rolapitant disrupted the interaction between OTUD3 and GRP78 by performing co-IP and GST pull-down assays."
38539203
reach
"Co-IP and GST pull-down assays confirmed that Rolapitant did not affect the interaction between OTUD3 and GRP78 (Fig. 3F, H)."
38539203
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"In lung cancer, OTUD3 interacts with GRP78, inhibiting cell growth and migration ( xref )."
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"All these results suggest that Rolapitant activates the ER stress-CHOP-DR5 pathway through modulating the OTUD3-GRP78 axis."
38539203
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"Therefore, inhibition of OTUD3-GRP78 signaling axis has been proposed as an anti-cancer therapeutic target in lung cancer."
38539203
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"The Rolapitant targets the OTUD3-GRP78 axis and displays DR5-induced anti-lung cancer activity in both in vitro and in vivo models."
38539203
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"This is further supported by the finding that the ubiquitin ligase CHIP targets OTUD3 for degradation, thereby suppressing the OTUD3-GRP78 signaling axis and inhibiting lung cancer metastasis [ xref ]."
41437362
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"Our in vitro and in vivo studies provide evidence that Rolapitant regulates ER stress through targeting the OTUD3-GRP78 axis to induce CHOP-DR5 signaling, exerting synergistic lethal effects with TRAIL on lung cancer."
38539203
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"For the first time, we demonstrated that the inhibition of OTUD3-GRP78 axis with Rolapitant induces ER stress-DR5-mediated extrinsic apoptosis to significantly inhibit the growth of human lung cancer."
38539203
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"These findings demonstrate that CHIP is a negative regulator of OTUD3 and CHIP suppresses lung cancer metastasis through inhibiting OTUD3-GRP78 signaling axis."
32483383
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"This finding underlines the potential of Rolapitant targeting the OTUD3-GRP78 axis in the clinical treatment of TRAIL-resistant lung cancers."
38539203
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"The interaction between OTUD3 and GRP78 observed in lung cancer H1299 cells was hardly detected in MCF7 cells (Supplementary Fig.  xref )."
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