IndraLab

Statements

OTUB2 binds CD274. 23 / 23
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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."
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"OTUB2 directly bound to PD-L1, hindering its ubiquitination and subsequent degradation within the endoplasmic reticulum."
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"Next, we characterized the interaction between OTUB2 and PD-L1."
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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."
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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)."
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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."
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"To detect the interaction between OTUB2 and PD-L1, we used a Duolink® in situ PLA kit (Sigma‒Aldrich, DUO92101)."
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"OTUB2 directly bound to PD-L1, hindering its ubiquitination and subsequent degradation within the endoplasmic reticulum."
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"Mechanistically, OTUB2 directly interacts with PD-L1 to disrupt the ubiquitination and degradation of PD-L1 in the endoplasmic reticulum."
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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."
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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."
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"OTUB2 interacts with the intracellular domain (ICD) of PD-L1."
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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 )."
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"Ectopically expressed OTUB2-WT but not catalytically inactive OTUB2 (C51S mutant) associated with PD-L1 in HEK293T cells (Fig.  xref )."
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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 )."
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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 )."
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"Next, we characterized the interaction between OTUB2 and PD-L1."
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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."
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"The PLA showed that PLA signals representing the OTUB2-PD-L1 interaction were mainly localized in the ER (Fig.  xref )."
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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."
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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 )."
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"OTUB2 can interact with PD-L1 and deubiquitinate and stabilize the PD-L1 protein by intervening in the ERAD pathway."
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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."
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