IndraLab

Statements

OTUB1 binds SMAD2_3. 20 / 20
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sparser
"Despite the phospho-dependent nature of OTUB1 interaction with SMAD2/3, no phospho-interaction motifs within OTUB1 have been reported."
24071738
reach
"The TGFbeta induced interaction between OTUB1 and SMAD2/3 was also confirmed in primary cells derived from mice (XREF_FIG)."
24071738
sparser
"Remarkably, endogenous OTUB1 interacts with SMAD2/3 only on TGFβ induction ( xref ), and the levels of phospho-SMAD2/3 on TGFβ stimulation directly correlate with the ability of OTUB1 to pull down SMAD2/3 ( xref )."
24071738
sparser
"The ligand inducible interaction between OTUB1 and phospho-SMAD2/3 indicates that OTUB1 could have a regulatory role in the TGFβ pathway."
24071738
reach
"3.7 OTUB1 interacts with active SMAD2/3 and impacts TGFbeta signalling."
25007997
sparser
"However, even in the absence of SMAD4, OTUB1 interacts with TGFβ-induced phospho-SMAD2/3, indicating that SMAD4 is not necessary to mediate phospho-SMAD2/3–OTUB1 interaction ( xref )."
24071738
sparser
"We also investigated the kinetics of OTUB1–SMAD2/3 interaction on TGFβ stimulation in HaCaT cells."
24071738
sparser
"Mutants were selected to either abolish OTUB1 catalytic activity or disrupt the interaction of OTUB1 with phospho-SMAD2/3."
24071738
sparser
"Consistent with the notion that OTUB1 interaction could be phospho-SMAD2/3-dependent, dephosphorylation of OTUB1 IPs by λ-phosphatase to dephosphorylate phospho-SMAD2/3 partially abolishes OTUB1–SMAD2/3 interaction ( xref )."
24071738
reach
"As shown in XREF_FIG, OTUB1 selectively binds components of the active phospho, SMAD2/3, and SMAD4 complex; however, it was not clear whether SMAD4 was required for this interaction."
24071738
reach
"Indeed, the tail phosphorylation dependent recruitment of OTUB1 to SMAD2/3 is a case for which interaction determinants are known XREF_BIBR."
25007997
sparser
"Therefore, the association of OTUB1 with phospho-SMAD2/3 would be predicted to prevent SMAD2/3 from being polyubiquitylated and degraded, thereby enhancing TGFβ signalling."
24071738
sparser
"These observations imply that SMAD4 is not required for the interaction between OTUB1 and phospho-SMAD2/3."
24071738
sparser
"These observations make OTUB1 a promising target for the development of small molecule inhibitors specifically targeting the OTUB1–SMAD2/3 interaction against diseases, such as cancer and fibrosis, where TGFβ signalling is abnormal."
24071738
sparser
"OTUB1 interacts with active SMAD2/3 and impacts TGFβ signalling."
25007997
reach
"Remarkably, endogenous OTUB1 interacts with SMAD2/3 only on TGFbeta induction (XREF_FIG), and the levels of phospho-SMAD2/3 on TGFbeta stimulation directly correlate with the ability of OTUB1 to pull down SMAD2/3 (XREF_FIG)."
24071738
sparser
"However, different from USP15, OTUB1 enhances TGF-β signaling by inhibiting the ubiquitination and degradation of active SMAD2/3 (and not the inactive un-phosphorylated form), because the association of OTUB1 to SMAD2/3 is phosphorylation dependent."
24756567
reach
"Despite the phospho dependent nature of OTUB1 interaction with SMAD2/3, no phospho-interaction motifs within OTUB1 have been reported."
24071738
sparser
"The findings shed light into the molecular mechanisms by which the phospho-SMAD2/3–OTUB1 interaction results in the regulation of TGFβ-induced transcription as well as phospho-SMAD2/3 turnover."
24071738
sparser
"It has been shown that OTUB1 interacts with phosphorylated Smad2/3 at the C-terminus specifically after TGF-β stimulation."
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