IndraLab

Statements

RNF31 binds OTULIN. 107 / 121
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"Thus, we wondered whether biotin-PD of OTULIN ABP can be used to monitor association of active substrate-bound OTULIN to HOIP, and potentially the entire LUBAC complex ( xref )."
28919039
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"Consistent with the structure, phosphorylation of Tyr56 prevents interaction between OTULIN and HOIP xref , xref (Fig. xref , bottom)."
26503766
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"The HOIP-OTULIN interaction can be disrupted by mutation of a critical residue (N102) in HOIP’s PUB domain ( xref )."
26670046
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"Phosphorylation dependent regulation of the interaction between OTULIN and HOIP offers an elegant additional layer of control for Met1 signalling."
26503766
sparser
"However, while the Y56D mutation decreased OTULIN interaction with HOIP, it enhanced OTULIN association with β-catenin (Fig.  xref and Supplementary Fig.  xref ), suggesting that OTULIN Tyr56 phosphorylation may promote OTULIN interaction with β-catenin."
32770022
reach
"Several studies have shown that OTULIN binds directly to the LUBAC subunit HOIP (Elliott etal, 2014; Schaeffer etal, 2014; Takiuchi etal, 2014)."
30804083
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No evidence text available
23708998
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"OTULIN interacts with HOIP via its PUB interacting motif (PIM), which binds to the N-terminal PUB domain of HOIP."
26085216
reach
"This posed the possibility for a very similar OTULIN binding mode to the HOIP PUB domain in comparison to p97 and the PNGase PUB domain.To further investigate the interaction between HOIP, OTULIN and [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24726327
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"LUBAC seems to be constantly active in cells, but the accumulation of Met1-Ub is continuously counterbalanced by OTULIN bound to HOIP."
25060092
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"This is in stark contrast to the interaction of HOIP with OTULIN, which was substantially increased by OTULIN overexpression ( xref C)."
27545878
sparser
"Phosphorylation of the highly conserved Tyr56 within the PIM was shown to disrupt the interaction between OTULIN and HOIP, which abrogates OTULIN-dependent suppression of LUBAC and enables LUBAC-regulated signaling."
32770022
sparser
"Regulating the HOIP‐OTULIN interaction."
26503766
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No evidence text available
28189684
biogrid
No evidence text available
24726323
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"The interaction of HOIP with OTULIN is also involved in OTULIN suppressing the canonical Wnt signaling pathway activation by LUBAC [ xref ]."
25972356
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No evidence text available
27458237
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"In glutathione S-transferase (GST) pull-down assays OTULIN bound to HOIP, but not to HOIL-1 or Sharpin ( Figure 2 A)."
24726327
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"OTULIN binds to the N-terminal PUB (PNGase/UBA or UBX-containing proteins) domain of HOIP via its PUB-interacting motif (PIM) and this interaction seems to be regulated by phosphorylation (Elliott et al., xref ; Schaeffer et al., xref ; Takiuchi et al., xref )."
31998699
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"Thus, the activity of HOIP and OTULIN complex in the activated receptor complexes might be necessary for an efficient and precise regulation of the NF-kappaB pathway."
24726327
sparser
"The interaction of HOIP with OTULIN is also involved in OTULIN suppressing the canonical Wnt signaling pathway activation by LUBAC."
24461064
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No evidence text available
23708998
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"While OTULIN binds HOIP directly through its PUB interacting motif (PIM), CYLD is recruited via a PIM in the bridging factor SPATA2."
28919039
sparser
"Whilst CYLD was recruited to TRAIL complex I and to the TRAIL‐induced necroptosis‐mediating complex in a HOIP‐dependent manner, OTULIN did not form part of these complexes (Fig  xref B and C)."
28258062
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"Furthermore, the direct binding of OTULIN and HOIP revealed the importance of their interaction for the proper action of the NF-κB signaling in vivo."
24726327
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"Despite the high-affinity, and seemingly more stable, interaction between HOIP and OTULIN, the interaction between HOIP and p97 was still significant and similar to other PUB-p97 interactions (XREF_FIG E)."
24726323
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No evidence text available
24726327
sparser
"These results implied that SC recruited HOIP was not associated with OTULIN, despite the fact that OTULIN and HOIP interacted prior to stimulation."
26670046
sparser
"OTULIN interacts with HOIP via its PUB‐interacting motif (PIM), which binds to the N‐terminal PUB domain of HOIP."
26085216
reach
"Importantly, the OTULIN peptide bound HOIP with 180nM affinity, a> 40-fold increase in comparison to p97 (XREF_FIG D)."
24726323
sparser
"OTULIN binding to HOIP is required to restrict LUBAC auto-ubiquitination, which is readily detected on HOIP, HOIL-1, and SHARPIN when OTULIN is depleted or mutated in its PIM ( xref , xref , xref , xref , xref )."
27591049
reach
"An interaction between HOIP and OTULIN or CYLD seems strange, since their highly specific yet counteracting activities would generate a futile energy consuming circle."
26503766
sparser
"It will be interesting to determine how OTULIN’s interaction with HOIP prevents its recruitment to SCs, e.g., whether OTULIN binding could interfere with HOIP’s ability to bind ubiquitin chains, a requirement for LUBAC recruitment to SCs ( xref , xref )."
26670046
sparser
"OTULIN binds to the PUB domain of HOIP and loss of HOIP-OTULIN interaction reduces OTULIN’s capacity to restrict LUBAC-induced immune responses [ xref ]."
27906774
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"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_BIBR] 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_BIBR]."
33288901
reach
"OTULIN also interacts with HOIP via its PUB interacting motif and inhibits LUBAC activity [XREF_BIBR, XREF_BIBR]."
33498196
sparser
"The OTULIN–HOIP interaction is also modulated by ubiquitination of OTULIN by the E3 ligase tripartite motif-containing protein 32 (TRIM32)."
33288901
sparser
"Recently, we found that TRIM32 conjugates nonproteolytic polyubiquitin onto OTULIN and the polyubiquitin blocks the interaction between HOIP and OTULIN, thereby activating NF-κB signaling [44] ."
33498196
biogrid
No evidence text available
24726327
sparser
"Gumby interacts with HOIP (also called RNF31), a key component of the linear ubiquitin assembly complex, and decreases linear ubiquitination and activation of NF-κB-dependent transcription."
23708998
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No evidence text available
24726323
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"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]."
33288901
sparser
"However, OTULIN Y56F, which cannot bind to HOIP, was reduced in its ability to block NF-κB signaling to a similar extent as the C129S catalytic mutant of OTULIN."
24726327
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No evidence text available
26670046
reach
"However, the kinases or phosphatases regulating the interaction between OTULIN and HOIP are still unknown."
26503766
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No evidence text available
26670046
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"Consistent with the structure, phosphorylation of Tyr56 prevents interaction between OTULIN and HOIP 60, 71."
26503766
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"OTULIN forms a complex with LUBAC through HOIP in unstimulated cells xref , xref , xref ."
32770022
sparser
"Loss of HOIP–OTULIN interaction reduces OTULIN capacity to restrict LUBAC-induced NF-kB activation ( xref )."
28469620
biogrid
No evidence text available
24726327
sparser
"Altogether, these data indicate that the direct binding of OTULIN to HOIP is important for its ability to limit NF-κB signaling activation."
24726327
sparser
"Moreover, a phospho-mimetic mutation on Tyr56 (Y56D) also abolished the association between OTULIN and HOIP, suggesting that genotoxic treatment may induce OTULIN phosphorylation at Tyr56, which disrupts the OTULIN-HOIP association."
32770022
reach
"Functionally, HOIP binding to OTULIN is required for the recruitment of OTULIN to the TNF receptor complex and to counteract HOIP dependent activation of the NF-kappaB pathway."
24726327
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"TNF stimulation, however, did not abolish the interaction between HOIP and OTULIN (XREF_FIG C and XREF_SUPPLEMENTARY A)."
26670046
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"We provide here the first demonstration that HOIP-OTULIN interact through the HOIP PUB domain and act as a bimolecular editing pair to regulate the NF-κB activation upon TNF stimulation."
24726327
reach
"OTULIN directly binds the LUBAC component HOIP, and knockdown of OTULIN in human cell lines increases M1 linked chains on LUBAC and its substrates."
27523608
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"Moreover, affinity measurements using ITC indicated that HOIP binding to OTULIN was stronger than for p97."
24726327
sparser
"Since both SPATA2 and OTULIN recognize the same binding motif in the PUB of HOIP, interaction of HOIP with SPATA2/CYLD and OTULIN is mutually exclusive [ xref , xref , xref , xref ]."
33288901
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No evidence text available
24726323
sparser
"OTULIN binds directly to the LUBAC subunit HOIP [ xref – xref ] and regulates LUBAC signalling, autoubiquitination, and stability [ xref , xref – xref ]."
32231246
sparser
"Functionally, HOIP binding to OTULIN is required for the recruitment of OTULIN to the TNF receptor complex and to counteract HOIP-dependent activation of the NF-κB pathway."
24726327
reach
"Together, these results show that CYLD and OTULIN interact with HOIP via the same or an overlapping site and that HOIP 's interactions with CYLD and OTULIN are mutually exclusive."
26670046
sparser
"OTULIN directly binds the LUBAC component HOIP, and knockdown of OTULIN in human cell lines increases M1-linked chains on LUBAC and its substrates ( xref , xref , xref , xref , xref )."
27523608
sparser
"OTULIN also interacts with HOIP via its PUB-interacting motif and inhibits LUBAC activity [ xref , xref ]."
33498196
sparser
"However, the kinases or phosphatases regulating the interaction between OTULIN and HOIP are still unknown."
26503766
reach
"Furthermore, the direct binding of OTULIN and HOIP revealed the importance of their interaction for the proper action of the NF-kappaB signaling in vivo.We investigated the interactome of LUBAC in sta[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24726327
sparser
"Recently, we found that TRIM32 conjugates nonproteolytic polyubiquitin onto OTULIN and the polyubiquitin blocks the interaction between HOIP and OTULIN, thereby activating NF-κB signaling [ xref ]."
33498196
sparser
"To investigate the functional consequences of the HOIP-OTULIN interaction, we analyzed the recruitment of OTULIN to the TNFR upon TNFα-mediated activation."
24726327
sparser
"Intriguingly, although the interaction of OTULIN with HOIP has been shown to be direct and was structurally characterized ( xref , xref ), we were not able to detect direct binding of CYLD to HOIP."
27545878
reach
"HOIP interacts with both CYLD and OTULIN even in unstimulated cells."
24461064
sparser
"Moreover, affinity measurements using ITC indicated that HOIP binding to OTULIN was stronger than for p97 ( Table 2 )."
24726327
biogrid
No evidence text available
24726327
sparser
"OTULIN also interacts with HOIP via its PUB-interacting motif and inhibits LUBAC activity [42, 43] ."
33498196
reach
"The OTULIN PIM binds HOIP with 40-fold greater affinity than a similar PIM from p97."
27913667
sparser
"This is also the case when OTULIN is phosphorylated at Tyr56 and in cells expressing the binding mutant OTULIN Y56F, both of which disrupt the OTULIN–HOIP interaction [ xref , xref ]."
33288901
reach
"The linear ubiquitin chain assembly complex (LUBAC) regulates immune signaling, and its function is regulated by the deubiquitinases OTULIN and CYLD, which associate with the catalytic subunit HOIP."
27591049
sparser
"Met1-linked ubiquitin (Met1-Ub) is assembled by the linear ubiquitin assembly complex (LUBAC), and this is counteracted by the Met1-Ub-specific deubiquitinase OTULIN, which binds to the catalytic LUBAC subunit HOIP."
26997266
reach
"It will be interesting to determine how OTULIN 's interaction with HOIP prevents its recruitment to SCs, e.g., whether OTULIN binding could interfere with HOIP 's ability to bind ubiquitin chains, a requirement for LUBAC recruitment to SCs."
26670046
reach
"TNFalpha stimulation promotes the recruitment of the HOIP and OTULIN complex to the active receptor complex, indicating that they can act as a bimolecular ubiquitin editing pair (ligase and DUB) impli[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24726327
sparser
"Several studies have shown that OTULIN binds directly to the LUBAC subunit HOIP (Elliott et al , xref ; Schaeffer et al , xref ; Takiuchi et al , xref )."
30804083
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"Although further experiments will be required to address these questions, ubiquitination could play an important role in regulating the interaction between HOIP and OTULIN."
24726327
reach
"OTULIN and CYLD bind HOIP in a mutually exclusive manner (71)."
35587511
reach
"LUBAC activity is counterbalanced by the Met1 specific deubiquitinase (DUB) OTULIN, which binds to the catalytic subunit HOIP via interactions between the HOIP peptide : N-glycanase and UBA- or UBX containing proteins (PUB) domain and a PUB interacting motif (PIM) in OTULIN."
26997266
biogrid
No evidence text available
27591049
reach
"Recently, we found that TRIM32 conjugates nonproteolytic polyubiquitin onto OTULIN and the polyubiquitin blocks the interaction between HOIP and OTULIN, thereby activating NF-kappaB signaling [XREF_BIBR]."
33498196
biogrid
No evidence text available
24726323
reach
"OTULIN binding to HOIP is required to restrict LUBAC auto-ubiquitination, which is readily detected on HOIP, HOIL-1, and SHARPIN when OTULIN is depleted or mutated in its PIM."
27591049
sparser
"Unlike these DUBs, which do not have a strict ubiquitin chain specificity, OTULIN (OTU deubiquitinase with linear specificity, also known as FAM105B or Gumby) binds the PUB domain of HOIP and selectively removes linear ubiquitin chains on LUBAC components thereby keeping uncontrolled TNF-associated inflammation in check ( xref ; xref ; xref ; xref ; xref )."
32671059
sparser
"Interestingly, OTULIN binds to the N-terminal PUB domain of HOIP through the PUB domain-interacting motif (PIM), and the phosphorylation of Tyr56 in the PIM of OTULIN abrogated the HOIP binding [ xref , xref , xref ]."
32403254
reach
"Phosphorylation of OTULIN 's tyrosine (Tyr) 56 prevents the binding of OTULIN to HOIP 97, 98."
26085216
reach
"Met1 linked ubiquitin (Met1-Ub) is assembled by the linear ubiquitin assembly complex (LUBAC), and this is counteracted by the Met1-Ub-specific deubiquitinase OTULIN, which binds to the catalytic LUBAC subunit HOIP."
26997266
sparser
"Although HOIP is able to interact with the AAA ATPase p97/valosin-containing protein (VCP) [ xref , xref ], which has recently been implicated in the recruitment of LUBAC to misfolded Huntingtin species [ xref ], the HOIP PUB domain binds OTULIN with a 40-fold higher affinity compared to p97/VCP and NMR-based in vitro studies indicate a more stable interaction between HOIP and OTULIN compared to p97/VCP [ xref ]."
33288901
sparser
"Further experiments found that TRIM32 conjugates polyubiquitin onto OTULIN and the polyubiquitin blocks the interaction between HOIP and OTULIN, thereby activating NF-κB signaling."
31504727
reach
"In line with recent reports, our data showed that prior to stimulation, both CYLD and OTULIN interacted with HOIP (XREF_SUPPLEMENTARY B-S1D)."
26670046
sparser
"Phosphorylation‐dependent regulation of the interaction between OTULIN and HOIP offers an elegant additional layer of control for Met1‐signalling (Fig. xref B)."
26503766
reach
"Altogether, these data indicate that the direct binding of OTULIN to HOIP is important for its ability to limit NF-kappaB signaling activation.In this study, we showed that the DUB OTULIN interacts wi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24726327
biogrid
No evidence text available
24726327
reach
"Aiming to find a mechanistic explanation for the unexpected absence of OTULIN from SCs, we first turned our attention to phosphorylation, as phosphorylation of OTULIN Tyr56 was previously reported to be capable of disrupting the interaction between HOIP and OTULIN."
26670046
biogrid
No evidence text available
26670046
biogrid
No evidence text available
24726323
reach
"An interaction between HOIP and OTULIN or CYLD at first inspection would seem contradictory, as a futile energy consuming cycle would exist."
27913667
reach
"Moreover, immunoprecipitation of SHARPIN copurified HOIP, HOIL-1 and OTULIN, and OTULIN interacted with HOIP in proteomic experiments, indicating that OTULIN may associate with HOIP and/or LUBAC."
24726323
sparser
"TNF stimulation, however, did not abolish the interaction between HOIP and OTULIN ( xref C and xref A)."
26670046
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No evidence text available
28244869
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No evidence text available
24726323
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"We wondered whether this depended on the formation of the OTULIN and HOIP complex or whether OTULIN would act in trans on the complex."
24726323
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"Importantly, even conservative mutation of the aforementioned cornerstone residue Asn102 to Asp (N102D) or Gln (N102Q) abolished HOIP binding to OTULIN (XREF_FIG I)."
24726323