IndraLab

Statements

OTUB2 binds CD274. 25 / 25
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"The authors of this study proposed that catalytically active OTUB2 binds to PD-L1 and prevents its degradation."
40427133
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"The compound OTUB2-IN1-1 inhibits the deubiquitinase activity of OTUB2 without affecting the physical interaction between OTUB2 and PD-L1."
39223632
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"OTUB2 directly bound to PD-L1, hindering its ubiquitination and subsequent degradation within the endoplasmic reticulum."
38638430
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"Next, we characterized the interaction between OTUB2 and PD-L1."
38167274
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"To ensure that the ability of OTUB2-IN-1 to reduce PD-L1 expression was due to the impaired deubiquitinase activity of OTUB2 rather than the impaired binding of OTUB2 to PD-L1, we further verified the ability of OTUB2-IN-1 to block the binding of OTUB2 to PD-L1 using a blocking chemiluminescence immunoassay (CLIA) and a co-IP assay."
38167274
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"We found that OTUB2-IN-1 did not interfere with protein interactions between OTUB2 and PD-L1 (Fig. 9g and Supplementary Fig. 21)."
38167274
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"The effects of OTUB2-IN-1 on blocking the interactions between OTUB2 and PD-L1 was determined by an indirect CLIA."
38167274
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"To detect the interaction between OTUB2 and PD-L1, we used a Duolink® in situ PLA kit (Sigma‒Aldrich, DUO92101)."
38167274
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"OTUB2 directly bound to PD-L1, hindering its ubiquitination and subsequent degradation within the endoplasmic reticulum."
38638430
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"Mechanistically, OTUB2 directly interacts with PD-L1 to disrupt the ubiquitination and degradation of PD-L1 in the endoplasmic reticulum."
38167274
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"An inhibitor of OTUB2, interfering with its deubiquitinase activity without disrupting the OTUB2-PD-L1 interaction, successfully reduces PD-L1 expression in tumor cells and suppressed tumor growth."
38167274
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"OTUB2 interacts with PD-L1 in the ER and to disrupt the ERAD of PD-L1 to impair T-lymphocyte-mediated antitumor immunity."
38167274
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"Compound 61 (also named OTUB1/USP8-IN-1), a dual OTUB1/USP8 inhibitor, effectively attenuates the growth of NSCLC cell lines in vivo . xref Unlike for OTUB1, specific inhibitors for OTUB2 have emerged that directly target PD-L1 to overcome tumor immune evasion by enhancing T cell-mediated cytotoxicity. xref The OTUB2-IN-1 was developed based on the OTUB2 binding pocket structure, reducing PD-L1 protein levels by inhibiting OTUB2’s catalytic activity (rather than blocking the OTUB2-PD-L1 interaction) and suppressing tumor growth. xref In parallel, an improved covalent inhibitor, LN5P45, has been developed for OTUB2, demonstrating excellent cellular target engagement and proteome-wide selectivity. xref These findings collectively validate OTUB2 as a promising target for cancer immunotherapy and provide valuable chemical tools for probing its biology."
41550777
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"OTUB2 can interact with PD-L1 and deubiquitinate and stabilize the PD-L1 protein by intervening in the ERAD pathway."
38167274
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"We demonstrated that OTUB2-IN-1 reduced PD-L1 protein turnover through inhibition of OTUB2 catalytic activity rather than blocking the OTUB2-PD-L1 interactions and exhibited strong growth-suppressive effects on multiple cancers by attenuating immunosuppression."
38167274
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"OTUB2 interacts with the intracellular domain (ICD) of PD-L1."
38167274
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"In line with this result, ectopically expressed OTUB2 associated with PD-L1 in HEK293T cells (Fig.  xref ), and E . coli -purified OTUB2 interacted with PD-L1 in vitro (Fig.  xref and Supplementary Fig.  xref )."
38167274
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"Ectopically expressed OTUB2-WT but not catalytically inactive OTUB2 (C51S mutant) associated with PD-L1 in HEK293T cells (Fig.  xref )."
38167274
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"We also observed that endogenous OTUB2 interacted with PD-L1 in multiple cell lines by using primary antibodies against either OTUB2 or PD-L1 (Fig.  xref and Supplementary Fig.  xref )."
38167274
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"To determine the subcellular location of the OTUB2-PD-L1 interacting complexes, we performed a Duolink in situ proximity ligation assay (PLA) and observed that the PLA signals were localized mainly in the cytoplasm (Fig.  xref and Supplementary Fig.  xref )."
38167274
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"Next, we characterized the interaction between OTUB2 and PD-L1."
38167274
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"To further explore the cellular location at which OTUB2 prevents the proteasomal degradation of PD-L1, we performed immunofluorescence (IF) following Duolink in situ PLAs using antibodies targeting different organelles to confirm the subcellular location of the OTUB2–PD-L1 interaction."
38167274
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"The PLA showed that PLA signals representing the OTUB2-PD-L1 interaction were mainly localized in the ER (Fig.  xref )."
38167274
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"To ensure that the ability of OTUB2-IN-1 to reduce PD-L1 expression was due to the impaired deubiquitinase activity of OTUB2 rather than the impaired binding of OTUB2 to PD-L1, we further verified the ability of OTUB2-IN-1 to block the binding of OTUB2 to PD-L1 using a blocking chemiluminescence immunoassay (CLIA) and a co-IP assay."
38167274
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"We found that OTUB2-IN-1 did not interfere with protein interactions between OTUB2 and PD-L1 (Fig.  xref and Supplementary Fig.  xref )."
38167274