IndraLab
Statements
sparser
"In contrast to these findings, Draber et al. demonstrated that, although both OTULIN and CYLD interact with HOIP under basal conditions, OTULIN is absent from RSCs [ xref ] (Fig. xref ) and that knock-out of OTULIN resulted in an increase of Met1-linked poly-Ub chains in the cytosol but not at TNFR1 or NOD2 RSCs [ xref ]."
reach
"Although HOIP is able to interact with the AAA ATPase p97 and valosin containing protein (VCP) [XREF_BIBR, XREF_BIBR], which has recently been implicated in the recruitment of LUBAC to misfolded Huntingtin species [XREF_BIBR], the HOIP PUB domain binds OTULIN with a 40-fold higher affinity compared to p97 and VCP and NMR based in vitro studies indicate a more stable interaction between HOIP and OTULIN compared to p97 and VCP [XREF_BIBR]."
sparser
"In contrast to these findings, Draber et al. demonstrated that, although both OTULIN and CYLD interact with HOIP under basal conditions, OTULIN is absent from RSCs [ xref ] (Fig. xref ) and that knock-out of OTULIN resulted in an increase of Met1-linked poly-Ub chains in the cytosol but not at TNFR1 or NOD2 RSCs [ xref ]."
reach
"Although HOIP is able to interact with the AAA ATPase p97 and valosin containing protein (VCP) [XREF_BIBR, XREF_BIBR], which has recently been implicated in the recruitment of LUBAC to misfolded Huntingtin species [XREF_BIBR], the HOIP PUB domain binds OTULIN with a 40-fold higher affinity compared to p97 and VCP and NMR based in vitro studies indicate a more stable interaction between HOIP and OTULIN compared to p97 and VCP [XREF_BIBR]."
OTULIN is modified
|
1
72
5
OTULIN is phosphorylated.
|
1
63
5
sparser
"Supporting this notion, the phosphorylation of Y56 in OTULIN is reported to increase after cells were induced to undergo necroptosis (by treatment with TNF + cycloheximide+ the pan-caspase inhibitor zVAD-fmk), and, the phosphatase DUSP14 was found to counteract the phosphorylation [59]."
sparser
"Supporting this notion, the phosphorylation of Y56 in OTULIN is reported to increase after cells were induced to undergo necroptosis (by treatment with TNF + cycloheximide+ the pan-caspase inhibitor zVAD-fmk), and, the phosphatase DUSP14 was found to counteract the phosphorylation [ xref ]."
sparser
"Additionally, DNA damage-induced ABL1/c-Abl (ABL proto-oncogene 1) activation can promote the phosphorylation of OTULIN, which enhances its interaction with β-catenin and promotes the activation of Wnt/β-catenin signalling ( xref ) This mechanism plays a critical role in the triple-negative breast cancer (TNBC) progression, metastasis, and drug resistance to cancer treatments ( xref ; xref ; xref )."
OTULIN is ubiquitinated.
|
7
OTULIN is dephosphorylated.
|
2
sparser
"Furthermore, while OTULIN and the HOIP PUB domain form a gel filtration‐stable complex in vitro , the majority of OTULIN in cell lysates does not coelute with LUBAC indicating that OTULIN may be phosphorylated in cells, and dephosphorylation of OTULIN in cell extracts led to coelution of OTULIN with LUBAC xref ."
sparser
"In contrast to these findings, Draber et al. demonstrated that, although both OTULIN and CYLD interact with HOIP under basal conditions, OTULIN is absent from RSCs [ xref ] (Fig. xref ) and that knock-out of OTULIN resulted in an increase of Met1-linked poly-Ub chains in the cytosol but not at TNFR1 or NOD2 RSCs [ xref ]."
sparser
"The mechanisms regulating the interaction of LUBAC with OTULIN and SPATA2-CYLD in cells are not well-understood but in vitro studies show that phosphorylation of the tyrosine (Y56) in the OTULIN PIM abrogates its interaction with HOIP, suggesting that this may be a mechanism to regulate the LUBAC–OTULIN complex [32]."
sparser
"The mechanisms regulating the interaction of LUBAC with OTULIN and SPATA2-CYLD in cells are not well-understood but in vitro studies show that phosphorylation of the tyrosine (Y56) in the OTULIN PIM abrogates its interaction with HOIP, suggesting that this may be a mechanism to regulate the LUBAC–OTULIN complex [ xref ]."
sparser
"Since the PUB domain mediates the interaction with CYLD and OTULIN (Schaeffer et al , xref ; Takiuchi et al , xref ; Draber et al , xref ) and the ZF and NZF1 are required for HOIP binding to ubiquitin and NEMO (Haas et al , xref ; Ikeda et al , xref ; Fujita et al , xref ), we hypothesised that cleavage of HOIP may modulate TRAIL‐induced gene activation."
reach
"It appears that OTULIN overexpression antagonizes NF-kappaB activation by removing Met1-polyUb, whereas OTULIN C129A acts as a high-affinity UBD that competes with other Met1 specific UBDs required for NF-kappaB signaling in a similar manner to the one recently reported for the overexpression of the NEMO UBAN domain."
reach
"Formation of the secondary, receptor-free cytoplasmic complex II is largely dependent on the activity of DUBs, specifically cylindromatosis (CYLD), A20 (also known as TNFAIP3) and ubiquitin thioesterase OTULIN, which destabilize complex I, abrogate NF-kappaB activation and release RIPK1 from complex I, which then forms the cytosolic complex II XREF_BIBR, XREF_BIBR."
reach
"Interestingly, overexpression of catalytically inactive OTULIN C129A also suppressed NF-kappaB signaling, in contrast to the Ub binding mutant OTULIN W96A, likely due to the ability of OTULIN C129A to compete with endogenous UBDs involved in NF-kappaB signaling, as it is the case for Ub binding domain in ABIN proteins and NEMO (UBAN)-based Met1 Ub sensors as well [XREF_BIBR, XREF_BIBR]."
reach
"To study whether the interaction of SNX27, OTULIN and Met1 linkage had any impact on NF-kappaB signalling activation, we first analysed TNFalpha induced NF-kappaB signalling activation in cells stably overexpressing SNX27 by checking the phosphorylation of key NF-kappaB signalling regulators."
| PMC
reach
"Immunoprecipitation in 293T cells and in vitro pull-down assays using bacterial recombinant proteins indicated that the direct interaction between SNX27 and OTULIN was mediated by the PDZ domain of SNX27 and the last 6 amino acids of OTULIN (Additional file 2 : Figure S2E-G), respectively."
| PMC
reach
"To study whether the interaction of SNX27, OTULIN and Met1 linkage had any impact on NF-kappaB signalling activation, we first analysed TNFalpha induced NF-kappaB signalling activation in cells stably overexpressing SNX27 by checking the phosphorylation of key NF-kappaB signalling regulators."
| PMC
reach
"Immunoprecipitation in 293T cells and in vitro pull-down assays using bacterial recombinant proteins indicated that the direct interaction between SNX27 and OTULIN was mediated by the PDZ domain of SNX27 and the last 6 amino acids of OTULIN (Additional file 2 : Figure S2E-G), respectively."
| PMC
sparser
"In‐depth biochemical analysis revealed how both OTULIN variants contribute to diminished OTULIN protein expression and defective hydrolysis of linear ubiquitin linkages observed in patient‐derived cells: whereas binding of OTULIN to linear ubiquitin was compromised by both variants, protein stability and catalytic activity was most affected by the OTULIN variant p."
reach
"In this study, the ‘deubiquitinase’ OTULIN was shown to restrict bacterial growth by controlling the density of linear ubiquitin chains on the bacterial surface, which serves as a platform for NF-κB activation.Finally, lattice light-sheet microscopy (LLSM) is a newly developed super-resolution microscopy method, which capitalises on previous microscopy techniques (light-sheet microscopy, SIM) and provides gentle and fast super-resolution in a volumetric sample13."
reach
"In this study, the ‘deubiquitinase’ OTULIN was shown to restrict bacterial growth by controlling the density of linear ubiquitin chains on the bacterial surface, which serves as a platform for NF-κB activation.Finally, lattice light-sheet microscopy (LLSM) is a newly developed super-resolution microscopy method, which capitalises on previous microscopy techniques (light-sheet microscopy, SIM) and provides gentle and fast super-resolution in a volumetric sample ."
sparser
"In‐depth biochemical analysis revealed how both OTULIN variants contribute to diminished OTULIN protein expression and defective hydrolysis of linear ubiquitin linkages observed in patient‐derived cells: whereas binding of OTULIN to linear ubiquitin was compromised by both variants, protein stability and catalytic activity was most affected by the OTULIN variant p."
sparser
"In contrast to these findings, Draber et al. demonstrated that, although both OTULIN and CYLD interact with HOIP under basal conditions, OTULIN is absent from RSCs [ xref ] (Fig. xref ) and that knock-out of OTULIN resulted in an increase of Met1-linked poly-Ub chains in the cytosol but not at TNFR1 or NOD2 RSCs [ xref ]."
sparser
"In contrast to these findings, Draber et al. demonstrated that, although both OTULIN and CYLD interact with HOIP under basal conditions, OTULIN is absent from RSCs [ xref ] (Fig. xref ) and that knock-out of OTULIN resulted in an increase of Met1-linked poly-Ub chains in the cytosol but not at TNFR1 or NOD2 RSCs [ xref ]."
OTULIN affects inflammatory response
|
15
OTULIN inhibits inflammatory response.
|
10
OTULIN activates inflammatory response.
|
5
sparser
"In contrast to these findings, Draber et al. demonstrated that, although both OTULIN and CYLD interact with HOIP under basal conditions, OTULIN is absent from RSCs [ xref ] (Fig. xref ) and that knock-out of OTULIN resulted in an increase of Met1-linked poly-Ub chains in the cytosol but not at TNFR1 or NOD2 RSCs [ xref ]."
sparser
"The mechanisms regulating the interaction of LUBAC with OTULIN and SPATA2-CYLD in cells are not well-understood but in vitro studies show that phosphorylation of the tyrosine (Y56) in the OTULIN PIM abrogates its interaction with HOIP, suggesting that this may be a mechanism to regulate the LUBAC–OTULIN complex [32]."
sparser
"The mechanisms regulating the interaction of LUBAC with OTULIN and SPATA2-CYLD in cells are not well-understood but in vitro studies show that phosphorylation of the tyrosine (Y56) in the OTULIN PIM abrogates its interaction with HOIP, suggesting that this may be a mechanism to regulate the LUBAC–OTULIN complex [ xref ]."
sparser
"The mechanisms regulating the interaction of LUBAC with OTULIN and SPATA2-CYLD in cells are not well-understood but in vitro studies show that phosphorylation of the tyrosine (Y56) in the OTULIN PIM abrogates its interaction with HOIP, suggesting that this may be a mechanism to regulate the LUBAC–OTULIN complex [32]."
sparser
"The mechanisms regulating the interaction of LUBAC with OTULIN and SPATA2-CYLD in cells are not well-understood but in vitro studies show that phosphorylation of the tyrosine (Y56) in the OTULIN PIM abrogates its interaction with HOIP, suggesting that this may be a mechanism to regulate the LUBAC–OTULIN complex [ xref ]."
sparser
"Nevertheless, simply mutating the catalytic Cys in DUBs to Ala or Ser, as used for A20 xref , xref , is problematic, as this potentially converts the DUB domain to a high‐affinity UBD; OTULIN C129A binds Met1‐diubiquitin with nanomolar affinity, and interferes with NF‐κB signalling in artificial ways xref ."
reach
"More strikingly, the structure also revealed that OTULIN is directly activated by the bound diubiquitin : placement of the proximal ubiquitin inserts the ubiquitin side chain of Glu16 directly into the active site of OTULIN, thereby pushing His339 into an active conformation and additionally co-ordinating the third catalytic residue, Asn341 (XREF_FIG)."
OTULIN affects cell death
|
1
10
OTULIN activates cell death.
|
6
OTULIN inhibits cell death.
|
1
4
reach
"Consistent with the finding that OTULIN overexpression was shown to delay NF-kappaB activation of TNF, whereas its knockdown was reported to increase the output of NF-kappaB signaling [XREF_BIBR, XREF_BIBR, XREF_BIBR], we found that OTULIN overexpression strongly depressed NF-kappaB activity and reduced the release of TNF-alpha, IL-1beta, and IL-6, which are the primary pro inflammatory cytokines that aggravate brain injury."
reach
"OTULIN overexpression significantly suppressed the production of TNF-alpha, IL-1beta, and IL-6 in PM and N9 cells via inhibiting the nuclear translocation of NF-kappaB p65 but had no effect on the pro inflammatory cytokines secreted by un activated microglia, which directly indicates that OTULIN suppressed microglia mediated neuroinflammation by inhibiting the NF-kappaB pathway and attenuated the release of inflammatory mediators under the in vitro ischemic condition."
OTULIN affects LUBAC
|
1
9
reach
"Formation of the secondary, receptor-free cytoplasmic complex II is largely dependent on the activity of DUBs, specifically cylindromatosis (CYLD), A20 (also known as TNFAIP3) and ubiquitin thioesterase OTULIN, which destabilize complex I, abrogate NF-kappaB activation and release RIPK1 from complex I, which then forms the cytosolic complex II XREF_BIBR, XREF_BIBR."
sparser
"In contrast, the interaction of OTULIN with β-catenin was substantially increased upon Dox treatment, which may be responsible for decreased linear ubiquitination and stabilization of β-catenin in cells exposed to genotoxic treatments (Supplementary Fig. xref , Fig. xref , lanes 1 and 2)."
sparser
"We speculate that the genotoxic stress-induced OTULIN phosphorylation at Tyr56 may not only increase the interaction between OTULIN and β-catenin but also enhance the LUBAC autoubiquitination and self-inhibition through dissociation from HOIP xref , which render OTULIN highly efficient in promoting β-catenin deubiquitination and stabilization upon DNA damage."
sparser
"Nevertheless, simply mutating the catalytic Cys in DUBs to Ala or Ser, as used for A20 xref , xref , is problematic, as this potentially converts the DUB domain to a high‐affinity UBD; OTULIN C129A binds Met1‐diubiquitin with nanomolar affinity, and interferes with NF‐κB signalling in artificial ways xref ."
reach
"When OTULIN was knocked down, IFN-I was no longer able to induce downregulation of STAT1 linear ubiquitination (Fig. 5f), suggesting that IFN-I-mediated removal of STAT1 linear ubiquitination is dependent on OTULIN.Given that IFN-I signaling utilized OTULIN to remove linear ubiquitination of STAT1, we speculated that overexpression of OTULIN could promote the binding of STAT1 to IFNAR2 in IFN-I signaling."
sparser
"In contrast, the interaction of OTULIN with β-catenin was substantially increased upon Dox treatment, which may be responsible for decreased linear ubiquitination and stabilization of β-catenin in cells exposed to genotoxic treatments (Supplementary Fig. xref , Fig. xref , lanes 1 and 2)."
sparser
"We speculate that the genotoxic stress-induced OTULIN phosphorylation at Tyr56 may not only increase the interaction between OTULIN and β-catenin but also enhance the LUBAC autoubiquitination and self-inhibition through dissociation from HOIP xref , which render OTULIN highly efficient in promoting β-catenin deubiquitination and stabilization upon DNA damage."
"Deubiquitination effects of swine OTULIN were identified. The interaction between porcine OTULIN and PRRSV Nsp11 is dependent on the OTU domain. PRRSV Nsp11 recruits OTULIN through a nonenzymatic combination to promote removal of linear ubiquitination targeting NEMO, resulting in a superimposed effect that inhibits the production of type I IFNs."
reach
"EA also enhanced microglial OTULIN expression in the present study, and OTULIN silencing effectively reversed the inhibitory effect of EA on microglial activation, as shown by the increased mean Iba-1 immunofluorescence intensity, which strongly indicates that enhanced OTULIN expression is necessary for EA to alleviate microglial activation."
LUBAC affects OTULIN
|
1
5
sparser
"Negative regulators of linear ubiquitination-dependent NF-κB activation have recently been reported, including the FAM105B (otulin) and CYLD linear ubiquitin-specific deubiquitinases (DUBs) and A20, which specifically binds the linear ubiquitin moiety and edits Rip1 ubiquitination to inhibit its activation ( xref ; xref ; xref ; xref ; xref )."
sparser
"Negative regulators of linear ubiquitination-dependent NF-κB activation have recently been reported, including the FAM105B (otulin) and CYLD linear ubiquitin-specific deubiquitinases (DUBs) and A20, which specifically binds the linear ubiquitin moiety and edits Rip1 ubiquitination to inhibit its activation ( xref ; xref ; xref ; xref ; xref )."
sparser
"The mechanisms regulating the interaction of LUBAC with OTULIN and SPATA2-CYLD in cells are not well-understood but in vitro studies show that phosphorylation of the tyrosine (Y56) in the OTULIN PIM abrogates its interaction with HOIP, suggesting that this may be a mechanism to regulate the LUBAC–OTULIN complex [32]."
sparser
"The mechanisms regulating the interaction of LUBAC with OTULIN and SPATA2-CYLD in cells are not well-understood but in vitro studies show that phosphorylation of the tyrosine (Y56) in the OTULIN PIM abrogates its interaction with HOIP, suggesting that this may be a mechanism to regulate the LUBAC–OTULIN complex [ xref ]."
OTULIN affects linear Ub chains
|
4
sparser
"The mechanisms regulating the interaction of LUBAC with OTULIN and SPATA2-CYLD in cells are not well-understood but in vitro studies show that phosphorylation of the tyrosine (Y56) in the OTULIN PIM abrogates its interaction with HOIP, suggesting that this may be a mechanism to regulate the LUBAC–OTULIN complex [32]."
sparser
"The mechanisms regulating the interaction of LUBAC with OTULIN and SPATA2-CYLD in cells are not well-understood but in vitro studies show that phosphorylation of the tyrosine (Y56) in the OTULIN PIM abrogates its interaction with HOIP, suggesting that this may be a mechanism to regulate the LUBAC–OTULIN complex [ xref ]."
OTULIN affects signal transduction
|
3
OTULIN inhibits signal transduction. 3 / 3
|
3
reach
"To further investigate whether enhanced OTULIN was required for EA to inhibit the NF-kappaB signalling pathway, OTULIN, p-IkappaBalpha, IkappaBalpha, cytoplasm-p65 and nucleus-p65 proteins from brain tissues in the ischaemic penumbra of the cerebral cortex were detected 24h after reperfusion."
OTULIN affects necroptotic process
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3
OTULIN inhibits necroptotic process.
|
2
OTULIN activates necroptotic process.
|
1
OTULIN activates necroptotic process. 1 / 1
|
1
OTULIN affects monoubiquitin
|
2
1
OTULIN binds monoubiquitin.
|
1
1
reach
"Interestingly, monoubiquitin binding to OTULIN did not induce rearrangement of the active site into a catalytically competent configuration 30, and monoubiquitin based suicide probes, where the C terminus of ubiquitin is replaced with a Cys reactive group 44, were unable to react with OTULIN, confirming that the catalytic triad in OTULIN was incompetent 29."
sparser
"Interestingly, monoubiquitin binding to OTULIN did not induce rearrangement of the active site into a catalytically competent configuration xref , and monoubiquitin‐based suicide probes, where the C terminus of ubiquitin is replaced with a Cys‐reactive group xref , were unable to react with OTULIN, confirming that the catalytic triad in OTULIN was incompetent xref ."
OTULIN activates monoubiquitin.
|
1
reach
"Recent evidence suggests that monoubiquitin release from its precursors is mediated predominantly by five main DUBs : ubiquitin thioesterase otulin, UCHL3, USP5, USP7 and USP9X [XREF_BIBR], although each has multiple substrates that can be targeted for deubiquitination to maintain the free ubiquitin pool."
OTULIN affects immune response
|
3
OTULIN affects apoptotic process
|
1
2
OTULIN inhibits apoptotic process.
|
1
1
OTULIN activates apoptotic process.
|
1
OTULIN activates apoptotic process. 1 / 1
|
1
OTULIN affects activity
|
3
OTULIN activates OTULIN.
|
2
OTULIN inhibits OTULIN.
|
1
OTULIN affects Met1-polyUb
|
3
OTULIN activates Met1-polyUb.
|
2
OTULIN inhibits Met1-polyUb.
|
1
reach
"It appears that OTULIN overexpression antagonizes NF-kappaB activation by removing Met1-polyUb, whereas OTULIN C129A acts as a high-affinity UBD that competes with other Met1 specific UBDs required for NF-kappaB signaling in a similar manner to the one recently reported for the overexpression of the NEMO UBAN domain."
OTULIN affects Met1
|
3
reach
"To study whether the interaction of SNX27, OTULIN and Met1 linkage had any impact on NF-kappaB signalling activation, we first analysed TNFalpha induced NF-kappaB signalling activation in cells stably overexpressing SNX27 by checking the phosphorylation of key NF-kappaB signalling regulators."
| PMC
reach
"Consistent with the finding that OTULIN overexpression was shown to delay NF-kappaB activation of TNF, whereas its knockdown was reported to increase the output of NF-kappaB signaling [XREF_BIBR, XREF_BIBR, XREF_BIBR], we found that OTULIN overexpression strongly depressed NF-kappaB activity and reduced the release of TNF-alpha, IL-1beta, and IL-6, which are the primary pro inflammatory cytokines that aggravate brain injury."
reach
"OTULIN overexpression significantly suppressed the production of TNF-alpha, IL-1beta, and IL-6 in PM and N9 cells via inhibiting the nuclear translocation of NF-kappaB p65 but had no effect on the pro inflammatory cytokines secreted by un activated microglia, which directly indicates that OTULIN suppressed microglia mediated neuroinflammation by inhibiting the NF-kappaB pathway and attenuated the release of inflammatory mediators under the in vitro ischemic condition."
OTULIN affects IKK_complex
|
1
2
OTULIN binds IKK_complex.
|
2
OTULIN inhibits IKK_complex.
|
1
Mutated OTULIN inhibits IKK_complex. 1 / 1
|
1
Met1 affects OTULIN
|
3
reach
"To study whether the interaction of SNX27, OTULIN and Met1 linkage had any impact on NF-kappaB signalling activation, we first analysed TNFalpha induced NF-kappaB signalling activation in cells stably overexpressing SNX27 by checking the phosphorylation of key NF-kappaB signalling regulators."
| PMC
reach
"EA also enhanced microglial OTULIN expression in the present study, and OTULIN silencing effectively reversed the inhibitory effect of EA on microglial activation, as shown by the increased mean Iba-1 immunofluorescence intensity, which strongly indicates that enhanced OTULIN expression is necessary for EA to alleviate microglial activation."
Valproic acid affects OTULIN
2
|
Valproic acid demethylates OTULIN.
1
|
Valproic acid decreases the amount of OTULIN.
1
|
Monoubiquitin affects OTULIN
|
1
1
reach
"Interestingly, monoubiquitin binding to OTULIN did not induce rearrangement of the active site into a catalytically competent configuration 30, and monoubiquitin based suicide probes, where the C terminus of ubiquitin is replaced with a Cys reactive group 44, were unable to react with OTULIN, confirming that the catalytic triad in OTULIN was incompetent 29."
sparser
"Interestingly, monoubiquitin binding to OTULIN did not induce rearrangement of the active site into a catalytically competent configuration xref , and monoubiquitin‐based suicide probes, where the C terminus of ubiquitin is replaced with a Cys‐reactive group xref , were unable to react with OTULIN, confirming that the catalytic triad in OTULIN was incompetent xref ."
Linear Ub chains affects OTULIN
|
2
Hsa-miR-6849-3p affects OTULIN
2
|
RNF31 affects PUB domain
|
2
reach
"Although HOIP is able to interact with the AAA ATPase p97 and valosin containing protein (VCP) [XREF_BIBR, XREF_BIBR], which has recently been implicated in the recruitment of LUBAC to misfolded Huntingtin species [XREF_BIBR], the HOIP PUB domain binds OTULIN with a 40-fold higher affinity compared to p97 and VCP and NMR based in vitro studies indicate a more stable interaction between HOIP and OTULIN compared to p97 and VCP [XREF_BIBR]."
OTULIN affects polyubiquitin chain
|
2
OTULIN affects cell population proliferation
|
2
OTULIN inhibits cell population proliferation.
|
1
OTULIN inhibits cell population proliferation. 1 / 1
|
1
OTULIN activates cell population proliferation.
|
1
OTULIN activates cell population proliferation. 1 / 1
|
1
OTULIN affects auto-linear ubiquitination
|
2
OTULIN affects Proteasome
|
2
OTULIN deubiquitinates Proteasome.
|
1
OTULIN deubiquitinates Proteasome. 1 / 1
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1
OTULIN activates Proteasome.
|
1
OTULIN activates Proteasome. 1 / 1
|
1
reach
"Although HOIP is able to interact with the AAA ATPase p97 and valosin containing protein (VCP) [XREF_BIBR, XREF_BIBR], which has recently been implicated in the recruitment of LUBAC to misfolded Huntingtin species [XREF_BIBR], the HOIP PUB domain binds OTULIN with a 40-fold higher affinity compared to p97 and VCP and NMR based in vitro studies indicate a more stable interaction between HOIP and OTULIN compared to p97 and VCP [XREF_BIBR]."
OTULIN affects Non-structural protein 4A
2
|
reach
"Similarly, the recently identified DUB OTULIN XREF_BIBR, XREF_BIBR, XREF_BIBR negatively regulates NOD2 mediated signalling by preventing LUBAC autoubiquitination under basal conditions, as well as restricting the accumulation of linear ubiquitin chains on RIP2 and LUBAC upon stimulation (Fig XREF_FIG)."
OTULIN affects NCIT:C19802
|
2
OTULIN ubiquitinates NCIT:C19802.
|
1
OTULIN ubiquitinates NCIT:C19802. 1 / 1
|
1
OTULIN binds NCIT:C19802.
|
1
OTULIN binds NCIT:C19802. 1 / 1
|
1
reach
"OTULIN overexpression significantly suppressed the production of TNF-alpha, IL-1beta, and IL-6 in PM and N9 cells via inhibiting the nuclear translocation of NF-kappaB p65 but had no effect on the pro inflammatory cytokines secreted by un activated microglia, which directly indicates that OTULIN suppressed microglia mediated neuroinflammation by inhibiting the NF-kappaB pathway and attenuated the release of inflammatory mediators under the in vitro ischemic condition."
reach
"Consistent with the finding that OTULIN overexpression was shown to delay NF-kappaB activation of TNF, whereas its knockdown was reported to increase the output of NF-kappaB signaling [XREF_BIBR, XREF_BIBR, XREF_BIBR], we found that OTULIN overexpression strongly depressed NF-kappaB activity and reduced the release of TNF-alpha, IL-1beta, and IL-6, which are the primary pro inflammatory cytokines that aggravate brain injury."
sparser
"e, f Co-immunoprecipitation and immunoblot analysis of extracts of HepG2.2.15 & HepG2 cells transfected with plasmid encoding Flag-OTULIN, Flag-OTULIN-K66-R and Hepatitis B virus (HBV) 1.3-fold genome plasmid (pHBV1.3) and treated with MG132, are shown
E3 ubiquitin ligases and deubiquitinases found to be significantly altered in response to HBV integration"
Non-structural protein 4A affects OTULIN
2
|
L18-MDP affects OTULIN
|
2
IKK_complex affects OTULIN
|
2
sparser
"e, f Co-immunoprecipitation and immunoblot analysis of extracts of HepG2.2.15 & HepG2 cells transfected with plasmid encoding Flag-OTULIN, Flag-OTULIN-K66-R and Hepatitis B virus (HBV) 1.3-fold genome plasmid (pHBV1.3) and treated with MG132, are shown
E3 ubiquitin ligases and deubiquitinases found to be significantly altered in response to HBV integration"
E3_Ub_ligase affects OTULIN
|
2
E3_Ub_ligase ubiquitinates OTULIN.
|
1
E3_Ub_ligase ubiquitinates OTULIN. 1 / 1
|
1
E3_Ub_ligase binds OTULIN.
|
1
E3_Ub_ligase binds OTULIN. 1 / 1
|
1
Trimellitic anhydride affects OTULIN
1
|
1
|
Naphthoquinone affects OTULIN
1
|
Hsa-miR-96-5p affects OTULIN
1
|
Hsa-miR-939-3p affects OTULIN
1
|
Hsa-miR-766-3p affects OTULIN
1
|
Hsa-miR-6860 affects OTULIN
1
|
Hsa-miR-6771-3p affects OTULIN
1
|
Hsa-miR-6720-5p affects OTULIN
1
|
Hsa-miR-661 affects OTULIN
1
|
Hsa-miR-6512-3p affects OTULIN
1
|
Hsa-miR-6501-3p affects OTULIN
1
|
Hsa-miR-616-5p affects OTULIN
1
|
Hsa-miR-612 affects OTULIN
1
|
Hsa-miR-548t-3p affects OTULIN
1
|
Hsa-miR-548s affects OTULIN
1
|
Hsa-miR-548c-3p affects OTULIN
1
|
Hsa-miR-548ay-3p affects OTULIN
1
|
Hsa-miR-548at-3p affects OTULIN
1
|
Hsa-miR-548as-3p affects OTULIN
1
|
Hsa-miR-548ap-3p affects OTULIN
1
|
Hsa-miR-548aa affects OTULIN
1
|
Hsa-miR-5189-5p affects OTULIN
1
|
Hsa-miR-508-5p affects OTULIN
1
|
Hsa-miR-4696 affects OTULIN
1
|
Hsa-miR-4684-5p affects OTULIN
1
|
Hsa-miR-451b affects OTULIN
1
|
Hsa-miR-3926 affects OTULIN
1
|
Hsa-miR-373-5p affects OTULIN
1
|
Hsa-miR-372-5p affects OTULIN
1
|
Hsa-miR-371b-5p affects OTULIN
1
|
Hsa-miR-371a-5p affects OTULIN
1
|
Hsa-miR-3675-3p affects OTULIN
1
|
Hsa-miR-3667-5p affects OTULIN
1
|
Hsa-miR-32-5p affects OTULIN
1
|
Hsa-miR-3190-5p affects OTULIN
1
|
Hsa-miR-3187-5p affects OTULIN
1
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Hsa-miR-29c-3p affects OTULIN
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Hsa-miR-196a-3p affects OTULIN
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Hsa-miR-16-5p affects OTULIN
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Hsa-miR-155-5p affects OTULIN
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Hsa-miR-1285-3p affects OTULIN
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Hsa-let-7a-5p affects OTULIN
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Hexabromocyclododecane affects OTULIN
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Enzyme inhibitor affects OTULIN
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Disheveled 2 affects OTULIN
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DiUb affects OTULIN
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Calcitriol affects OTULIN
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Bisphenol A affects OTULIN
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Autosomal recessive mutations affects OTULIN
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Anti-TNF/Infliximab affects OTULIN
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Anti-TNF neutralizing antibodies affects OTULIN
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Acrylamide affects OTULIN
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WT-, S165A-, affects OTULIN
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Vehicle Emissions affects OTULIN
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Ubiquitin affects Ser65
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Tobacco Smoke Pollution affects OTULIN
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Ser65 affects Ubiquitin
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SNX27 affects PDZ domain
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"Immunoprecipitation in 293T cells and in vitro pull-down assays using bacterial recombinant proteins indicated that the direct interaction between SNX27 and OTULIN was mediated by the PDZ domain of SNX27 and the last 6 amino acids of OTULIN (Additional file 2 : Figure S2E-G), respectively."
| PMC
SNX27 affects Met1
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"To study whether the interaction of SNX27, OTULIN and Met1 linkage had any impact on NF-kappaB signalling activation, we first analysed TNFalpha induced NF-kappaB signalling activation in cells stably overexpressing SNX27 by checking the phosphorylation of key NF-kappaB signalling regulators."
| PMC
S165D-SHARPIN affects OTULIN
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Results EA affects OTULIN
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eidos
"Results EA enhanced OTULIN expression following focal cerebral ischaemia / reperfusion injury To detect the effects of EA on the time course of OTULIN expression , OTULIN mRNA and protein in the ischaemic penumbra of the cerebral cortex ( Fig. 2a ) were measured from 2 h to 7 days after reperfusion using RT-qPCR and Western blotting , respectively ."
Replicase polyprotein 1a affects OTULIN
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OTULIN binds Replicase polyprotein 1a. 1 / 1
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RNF31 affects Met55
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RNF31 affects Met1
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Porcine Reproductive and Respiratory Syndrome increases the amount of OTULIN. 1 / 1
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PRRSV non-structural protein 11 affects OTULIN
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PRRSV infection affects OTULIN
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PR-619 affects OTULIN
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PDZ domain affects SNX27
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"Immunoprecipitation in 293T cells and in vitro pull-down assays using bacterial recombinant proteins indicated that the direct interaction between SNX27 and OTULIN was mediated by the PDZ domain of SNX27 and the last 6 amino acids of OTULIN (Additional file 2 : Figure S2E-G), respectively."
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OTULIN affects signaling
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OTULIN affects pyridoxamine
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OTULIN inhibits pyridoxamine. 1 / 1
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"OTULIN overexpression significantly suppressed the production of TNF-alpha, IL-1beta, and IL-6 in PM and N9 cells via inhibiting the nuclear translocation of NF-kappaB p65 but had no effect on the pro inflammatory cytokines secreted by un activated microglia, which directly indicates that OTULIN suppressed microglia mediated neuroinflammation by inhibiting the NF-kappaB pathway and attenuated the release of inflammatory mediators under the in vitro ischemic condition."
OTULIN affects polyubiquitin chains
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OTULIN affects phosphorylation
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OTULIN affects linear ubiquitination RIP2
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eidos
"Similarly , the DUB Ovarian Tumor Deubiquitinase With Linear Linkage Specificity ( OTULIN ) which hydrolyses linear ubiquitin chains synthesized on RIP1 by LUBAC in TNF-signaling pathways [ 188 ] , was identified to restrict linear ubiquitination of RIP2 , attenuating signaling downstream of NOD2 [ 185 ] ."
OTULIN affects innate immune response
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OTULIN inhibits innate immune response. 1 / 1
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OTULIN affects independent functions
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OTULIN affects highlight novel ubiquitin-dependent
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OTULIN affects hepatocellular carcinoma
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OTULIN inhibits hepatocellular carcinoma. 1 / 1
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OTULIN affects doxycycline
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OTULIN activates doxycycline. 1 / 1
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OTULIN affects disheveled 2
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OTULIN affects diUb
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OTULIN affects cellular Met1-linked Ub
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OTULIN affects cell fate control
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OTULIN affects autoubiquitylation
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OTULIN affects autophagy maturation
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OTULIN affects autophagy initiation
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OTULIN affects auto-inflammatory syndrome
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OTULIN affects astrogliosis
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OTULIN affects anti-TNF neutralizing antibody
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OTULIN affects abundance linear chains
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OTULIN affects WT-, S165A-,
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OTULIN affects Ub chains attached IRAK1
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OTULIN affects TNFR1 complex
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OTULIN affects TCR-mediated NF-kappaB
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OTULIN affects Spinal Cord Injuries
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OTULIN activates Spinal Cord Injuries. 1 / 1
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OTULIN affects Skin Diseases
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OTULIN activates Skin Diseases. 1 / 1
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OTULIN affects STAT1-IFNAR2
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OTULIN affects STAT1-IFNAR2 interaction
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OTULIN affects S165D-SHARPIN
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OTULIN affects Replicase polyprotein 1a
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OTULIN binds Replicase polyprotein 1a. 1 / 1
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OTULIN affects RIPK1-mediated keratinocyte necroptosis
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OTULIN affects RIPK1 ubiquitin
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OTULIN affects Panniculitis
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OTULIN activates Panniculitis. 1 / 1
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OTULIN affects PRRSV non-structural protein 11
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"Immunoprecipitation in 293T cells and in vitro pull-down assays using bacterial recombinant proteins indicated that the direct interaction between SNX27 and OTULIN was mediated by the PDZ domain of SNX27 and the last 6 amino acids of OTULIN (Additional file 2 : Figure S2E-G), respectively."
| PMC
OTULIN affects OTULIN-HOIP
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"Multiple DUBs from the human ovarian tumor (OTU) DUB family that display various degrees of specificities towards different ubiquitin linkage types have been identified and can be used for UbiCRest: For instance, OTUB1 specifically cleaves K48-, OTUD1 K63-, Cezanne K11-, and OTULIN M1-linked ubiquitylation, whereas OTUD3 displays specificity towards K6- and K11-linked ubiquitylation ( xref )."
OTULIN affects OTU domain
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OTULIN affects Neoplasm Metastasis
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OTULIN activates Neoplasm Metastasis. 1 / 1
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OTULIN affects Neoplasm Invasiveness
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OTULIN inhibits Neoplasm Invasiveness. 1 / 1
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OTULIN affects NF-kappaB-responsive genes
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OTULIN affects NF-kappaB activation pathway
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OTULIN affects Met55
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OTULIN affects Met1-Ub
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OTULIN affects MAPK cascade
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OTULIN activates MAPK cascade. 1 / 1
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OTULIN affects M1-ubiquitin
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OTULIN affects M1-Ubiquitin
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OTULIN affects M1 polyubiquitination
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OTULIN affects LUBAC-
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OTULIN affects LIVER-INFLAMMATION
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OTULIN affects Jurkat Cells
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OTULIN inhibits Jurkat Cells. 1 / 1
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OTULIN affects JM8A3.N1
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"Otulin and Fam105b targeted JM8A3.N1 (C57BL/6 background strain) ES cells (Fam105b tm1a (EUCOMM) Hmgu) were obtained from EUCOMM and used to generate mice bearing neomycin selection and LacZ cassettes and a loxP flanked exon 3 of Otulin, termed the targeted " LacZ " or " LZ " allele (see also XREF_FIG)."
OTULIN affects Interferon
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OTULIN bound to Nsp11 inhibits Interferon. 1 / 1
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OTULIN affects IFN-regulatory transcription
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OTULIN affects IFN-I-mediated STAT1 activation
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OTULIN affects IFN-I
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"Interestingly, liver inflammation observed in OTULIN deficient mice is accompanied by increased expression of IFN response genes [XREF_BIBR] and murine Otulin C129A and C129A Ripk3 -/- Casp8 -/- BMDMs show spontaneous activation of IKKepsilon and TANK binding kinase 1 (TBK1) [XREF_BIBR], indicating that OTULIN suppresses IFN-I production pathways."
OTULIN affects IFN-I pathways
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"Interestingly , liver inflammation observed in OTULIN-deficient mice is accompanied by increased expression of IFN response genes [ 68 ] and murine OtulinC129A / C129A Ripk3 - / - Casp8 - / - BMDMs show spontaneous activation of IKKepsilon and TANK-binding kinase 1 ( TBK1 ) [ 23 ] , indicating that OTULIN suppresses IFN-I production pathways ."
OTULIN affects HEPATOCELLULAR-CARCINOMA
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OTULIN inhibits HEPATOCELLULAR-CARCINOMA. 1 / 1
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OTULIN affects E3_Ub_ligase
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E3_Ub_ligase binds OTULIN. 1 / 1
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OTULIN affects E3 ligase function106
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"Since the PUB domain mediates the interaction with CYLD and OTULIN (Schaeffer et al , xref ; Takiuchi et al , xref ; Draber et al , xref ) and the ZF and NZF1 are required for HOIP binding to ubiquitin and NEMO (Haas et al , xref ; Ikeda et al , xref ; Fujita et al , xref ), we hypothesised that cleavage of HOIP may modulate TRAIL‐induced gene activation."
OTULIN ABP affects OTULIN
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OTU domain affects OTULIN
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NCIT:C19802 affects OTULIN
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OTULIN binds NCIT:C19802. 1 / 1
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Met55 affects RNF31
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Met1 affects SNX27
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"To study whether the interaction of SNX27, OTULIN and Met1 linkage had any impact on NF-kappaB signalling activation, we first analysed TNFalpha induced NF-kappaB signalling activation in cells stably overexpressing SNX27 by checking the phosphorylation of key NF-kappaB signalling regulators."
| PMC
Met1 affects RNF31
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"To study whether the interaction of SNX27, OTULIN and Met1 linkage had any impact on NF-kappaB signalling activation, we first analysed TNFalpha induced NF-kappaB signalling activation in cells stably overexpressing SNX27 by checking the phosphorylation of key NF-kappaB signalling regulators."
| PMC
Met1 affects CYLD
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LUBAC- affects OTULIN
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K66R be key ubiquitination site K48-linked poly-ubiquitination affects OTULIN
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Infections affects OTULIN
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Infections increases the amount of OTULIN. 1 / 1
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Drugs, Chinese Herbal affects OTULIN
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sparser
"Since the PUB domain mediates the interaction with CYLD and OTULIN (Schaeffer et al , xref ; Takiuchi et al , xref ; Draber et al , xref ) and the ZF and NZF1 are required for HOIP binding to ubiquitin and NEMO (Haas et al , xref ; Ikeda et al , xref ; Fujita et al , xref ), we hypothesised that cleavage of HOIP may modulate TRAIL‐induced gene activation."
sparser
"Since the PUB domain mediates the interaction with CYLD and OTULIN (Schaeffer et al , xref ; Takiuchi et al , xref ; Draber et al , xref ) and the ZF and NZF1 are required for HOIP binding to ubiquitin and NEMO (Haas et al , xref ; Ikeda et al , xref ; Fujita et al , xref ), we hypothesised that cleavage of HOIP may modulate TRAIL‐induced gene activation."
C646 compound affects OTULIN
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