IndraLab

Statements

OTUB1 binds GPX4. 34 / 34
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"By addressing these limitations, future studies will further elucidate the therapeutic potential of the OTUB1-GPX4 axis and validate its role in ferroptosis regulation across diverse CRC models."
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"Allosteric modulators like β-elemene selectively disrupt OTUB1-GPX4 interactions to induce ferroptosis in gastric cancer without systemic toxicity [ xref ]."
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"Targeting the OTUB1-GPX4 axis represents a novel therapeutic strategy that could sensitize CRC cells to ferroptosis and improve treatment outcomes."
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"The findings suggest that targeting the OTUB1-GPX4 axis could represent a new therapeutic approach, particularly in overcoming resistance to conventional treatments."
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"Mechanistic analysis revealed that β-elemene disrupts the OTUB1-GPX4 interaction, leading to increased GPX4 ubiquitination and degradation, thus promoting ferroptosis."
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No evidence text available
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"Previous studies have demonstrated that in GC cell lines, OTUB1 can form a complex with GPX4, thereby reducing the ubiquitination levels of GPX4 and inhibiting its proteasomal degradation ( xref )."
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"IF assays confirmed the co-localization of OTUB1 with GPX4 ( xref ), and COIP assays showed that the interaction between GPX4 and OTUB1 was robust in both the control and the radiotherapy-alone groups."
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"Our study revealing that β-elemene reverses radioresistance in GC cells primarily by promoting ferroptosis through the inhibition of the OTUB1-GPX4 interaction."
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"The findings indicate that β-elemene disrupts the GPX4-OTUB1 axis, likely through allosteric modulation or competitive inhibition ( xref )."
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"Gaining such detailed molecular insights will aid in developing targeted therapies that exploit the reliance of radioresistant GC cells on the GPX4-OTUB1 interaction."
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"Conversely, β-caryophyllene disrupts OTUB1-GPX4 binding in gastric cancer, triggering K48-linked GPX4 degradation to induce ferroptosis [ xref ]."
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"The results indicated that only OTUB1 could bind to GPX4 (Fig. xref )."
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"Next, we co-transfected Myc-tagged CST1 and Flag-tagged OTUB1, the results showed that in the absence of OTUB1, CST1 could bind to GPX4 (Fig. xref , lane 2); in the absence of CST1, OTUB1 could also bind to GPX4 (Fig. xref , lane 3); and when OTUB1-Flag was transfected at the same time, OTUB1 bound to GPX4 was significantly increased upon CST1-Myc (Fig. xref , lane 4)."
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"Co-IP assay confirmed that OTUB1 interacted with GPX4 and prevented its ubiquitin-mediated degradation, thereby stabilizing GPX4."
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"The interaction of GPX4 with OTUB1 prevents its ubiquitination and degradation, thereby enhancing its stability."
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"Co-immunoprecipitation (Co-IP) assay was performed to confirm the interaction between OTUB1 and GPX4."
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"By recruiting OTUB1, which binds to GPX4, CST1 inhibits the ubiquitination and degradation of GPX4 protein, promotes protein stability, reduces intracellular reactive oxygen species, and protects cells against ferroptosis."
36369321
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"Coomassie blue staining and mass spectrometry analysis suggested that OTUB1 might interact with GPX4 (Fig. xref I)."
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"Targeting the OTUB1-GPX4 axis may provide a new therapeutic approach for inducing ferroptosis in CRC cells, potentially overcoming resistance to conventional therapies and improving patient outcomes."
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"Through Co-IP experiments, we found that OTUB1 could interact with the GPX4 protein (Fig. xref M-O)."
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"Then PDBePISA was used online, the interaction surface in the protein complex was analyzed, and it was found that the free energy of binding between CST1, OTUB1 and GPX4 was low (Fig. S4B), indicating that a stable complex can be formed between them."
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"This OTUB1-GPX4 axis has been linked to ferroptosis resistance in other cancer types, however, its role in CRC remains unexplored."
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"OTUB1 interacted with GPX4 and upregulates GPX4 protein levels by modulating ubiquitination."
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"By recruiting OTUB1, which binds to GPX4, CST1 inhibits the ubiquitination and degradation of GPX4 protein, promotes protein stability, reduces intracellular reactive oxygen species, and protects cells against ferroptosis."
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"Co-IP experiments demonstrated a direct interaction between OTUB1 and GPX4 in SW620 cells (Fig.  xref B)."
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"Moreover, the observed reduction in GPX4 levels following OTUB1 knockdown, along with the rescue of cell viability through GPX4 overexpression, highlights the critical role of the OTUB1-GPX4 axis in ferroptosis regulation."
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"This suggests that targeting the OTUB1-GPX4 axis could disrupt this protective mechanism, sensitize CRC cells to ferroptosis, and improve the efficacy of therapies aimed at inducing oxidative stress [ xref ]."
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"While SW620 is a robust model due to its specific Kras and p53 mutations, future studies should include additional CRC cell lines with diverse genetic backgrounds, such as HT29 (BRAF V600E, p53 R273H) and HCT116 (KRAS G13D, wild-type p53), to determine whether the OTUB1-GPX4 regulatory axis is influenced by specific mutational contexts."
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"The results indicated that only OTUB1 could bind to GPX4 (Fig. 4C)."
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"Next, we co-transfected Myc-tagged CST1 and Flag-tagged OTUB1, the results showed that in the absence of OTUB1, CST1 could bind to GPX4 (Fig. 4D, lane 2); in the absence of CST1, OTUB1 could also bind to GPX4 (Fig. 4D, lane 3); and when OTUB1-Flag was transfected at the same time, OTUB1 bound to GPX4 was significantly increased upon CST1-Myc (Fig. 4D, lane 4)."
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"Moreover, emerging evidence indicates that OTUB1 interacts with GPX4 to prevent its ubiquitin-mediated degradation, enhancing its stability and protecting cancer cells from ferroptosis [ xref , xref ]."
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"Current strategies address these through catalytic inhibition (e.g., MLN4924 targeting NEDD8-activation [ xref ]), allosteric modulation (e.g., β-elemene disrupting OTUB1-GPX4 binding [ xref ]), and epigenetic reprogramming (e.g., OTUD4 demethylation to restore ATM signaling [ xref ])."
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