IndraLab

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OTUD5 binds DBC1. 21 / 21
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sparser
"Lots of interaction assays suggested that the potential DUB OTUD5 might interact with DBC1 ( xref ) and regulate its ubiquitination ( xref )."
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sparser
"Co-IP analysis demonstrated the exogenous interaction between OTUD5 and DBC1 ( xref )."
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sparser
"Furthermore, we confirmed that endogenous DBC1 could directly interact with OTUD5 ( xref , xref ), which was further verified by an in vitro pull-down assay using purified His-tagged DBC1 to pull down OTUD5 from cell lysates ( xref , xref )."
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sparser
"Interestingly, we found that either hypoxia treatment or overexpression of SIAH2 promoted the interaction between DBC1 and SIAH2, but inhibited the interaction of DBC1 with OTUD5 ( xref , xref )."
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sparser
"Moreover, we still need to further investigate the details of how the OTUD5-DBC1 complex dissociates under hypoxia to modulate DBC1 stability."
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sparser
"Figure 4: the authors should study OTUD5 binding to DBC1 under hypoxia compared with normoxia to substantiate the claim for preferred interaction under normoxia."
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sparser
"The authors propose that in normoxia, OTUD5 is bound to DBC1 which is displaced by SIAH2 upon activation by hypoxia, however despite the comprehensive study of the interaction between DBC1 this is not fully supported by the data."
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sparser
"1) The authors propose a hypothesis that OTUD5 is bound to DBC1 in normoxic conditions which is displaced upon activation of SIAH2."
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sparser
"Does OTUD5 bind to non-ubiquitinated DBC1?"
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sparser
"Direct binding of recombinant DBC1 and OTUD5 could confirm this."
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sparser
"As shown in the new Figure 4I, we found that the deubiquitinase OTUD5 only interacted with DBC1 under normoxic conditions, and the interaction between SIAH2 and DBC1 was increased under hypoxia, which promoted the ubiquitination and degradation of DBC1."
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sparser
"We further analyzed the interaction of OTUD5 with DBC1 in SIAH2 knockout cells, and showed that deletion of SIAH2 significantly increased the interaction of OTUD5 with DBC1 under hypoxic conditions (new Figure 4I)."
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sparser
"We showed that OTUD5 binds to and deubiquitinates DBC1 under normoxia, leading to enhanced protein stability of DBC1."
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sparser
"However, such OTUD5-DBC1 interaction is attenuated under hypoxia by multiple mechanisms."
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sparser
"First, SIAH2 could attenuate endogenous OTUD5-DBC1 interaction under hypoxic conditions, while deletion of SIAH2 significantly increased the interaction of OTUD5 with DBC1 under hypoxia (new Figure 4I)."
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"We analyzed the interaction of endogenous OTUD5 and DBC1 under normoxia and hypoxia."
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"The result showed that OTUD5 only interacted with DBC1 under normoxia in WT cells."
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sparser
"These results suggest that, under hypoxic conditions, the interaction between SIAH2 and DBC1 attenuates OTUD5 binding to DBC1, and the degradation of OTUD5 further reduces its interaction with DBC1."
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sparser
"We performed the study and found that deletion of SIAH2 significantly increased the interaction of OTUD5 with DBC1 under hypoxia (new Figure 4I)."
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sparser
"These results suggest that under hypoxic conditions the interaction between SIAH2 and DBC1 attenuates OTUD5 binding to DBC1."
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sparser
"And as shown in the new Figure 4I, OTUD5 interacted with DBC1 under normoxic conditions."
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