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CYLD deubiquitinates RIPK1. 67 / 67
1 | 66
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"Deubiquitination of RIP by over-expressed CYLD was abrogated in optineurin knockdown cells."
21408173
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"Then, a tumor suppressor cylindromatosis (CYLD) protein promotes the deubiquitination of RIP1 in either complex I or complex II."
28789335
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"It does this by binding to ubiquitinated RIP (receptor interacting protein) to displace IKBKG (inhibitor of kappaB kinase gamma), and then bringing in cylindromatosis (CYLD) to deubiquitinate RIP and terminate the signaling pathway XREF_BIBR - XREF_BIBR."
25329564
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"In the course of complex II formation, RIP1 deubiquitination by CYLD, a deubiquitinase that cleaves linear- and K63-ubiquitin chains, plays a crucial role."
33815386
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"CYLD can deubiquitinate RIPK1, freeing it to be phosphorylated and complex with RIPK3 (Complex IIb) to form the necrosome [XREF_BIBR - XREF_BIBR]."
25342597
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"RIPK1 ubiquitylation can be restricted by cIAP inhibition or by the deubiquitylase activity of CYLD, which is recruited to the complex-I through the LUBAC binding protein SPATA2 XREF_BIBR - XREF_BIBR."
29449584
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"[XREF_BIBR] CYLD deubiquitination of TRAF6, RIP1, and NF-kappaB-essential modulator (NEMO) leads to inactivation of NF-kappaB signaling."
25025000
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"The suppression of CYLD by overexpression of LEF-1 stimulates sustained ubiquitination of RIPK1, causing the defection of necroptosis and survival of CLL cells."
32764983
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"The deubiquitination of RIPK1 by CYLD is critical for the activation of necroptosis and complex II formation [16]."
31752870
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"It regulates NF-kappaB signaling by facilitating deubiquitination of ubiquitinated RIP by CYLD [7,14]."
23811275
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"Taken together, these results indicate that selenite triggered upregulation of CYLD transcription induced RIP1 deubiquitination and apoptosis."
24577083
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"Deubiquitination of RIP1 by CYLD in the necrosome was also suggested to facilitate necroptosis [XREF_BIBR]."
33432113
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"Indeed, RIP1 polyubiquitination leads to NF-kappaB activation and promotes cell survival, whereas deubiquitination of RIP1 by CYLD promotes the assembly of the cytosolic complex termed Ripoptosome, which leads to cell death."
22435549
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"We conclude that PrP traps CYLD, preventing it from binding and deubiquitinating RIP1 and TRAF2."
28900035
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"Necroptosis can be initiated by activation of Toll like receptors (TLR) 3 and 4, TNF-alpha receptor 1 or, as more recently shown by us and others, by cylindromatosis (CYLD)-mediated deubiquitination of RIPK1 [XREF_BIBR]."
| PMC
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"TNFR1 activation together with the absence of c-IAPs (IAP antagonist treatment), translation inhibition (cyclohexamide treatment), or RIP1 deubiquitination by the deubiquitinating enzyme (DUB) CYLD may promote the translocation of RIP1 to a secondary cytoplasmatic complex, Complex II [XREF_BIBR - XREF_BIBR]."
26045969
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"This assumption is strengthened by our results which show that overexpressed CYLD fails to deubiquitinate RIP and inhibit TNFalpha induced NF-kappaB activation in presence of H486R mutant."
21408173
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"Conversely, disrupting CYLD phosphorylation using IKK inhibitors reactivates CYLD, which in turn, deubiquitinates and switches RIPK1 into a death-signaling molecule (Fig. 8b)."
32024820
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"When RIPK1 is not ubiquitinated, complex IIb is formed; in order for this to occur, the cylindromatosis tumour suppressor protein DUB (CYLD) enzyme deubiquitinates RIPK1, thereby allowing it to disassociate from complex I 42 and form complex IIb, whereby TRADD is replaced by RIPK3, upon degradation of cIAP1 and 2 XREF_BIBR, XREF_BIBR, XREF_BIBR."
30755793
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"Does CYLD require ubiquitin binding adaptors to inhibit RIP1 ubiquitination?"
21119682
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"In the presence of Smac mimetic, cIAP1/2 are degraded and this process promotes the deubiquitination of RIPK1 by CYLD."
32411707
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"We reveal that CYLD deubiquitinates RIP1 to facilitate TNF induced necrosis."
24098568
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"Cyld can deubiquitylate RIPK1 and facilitate TNF-induced necroptosis, which can be cleaved by caspase 8 ."
30442927
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"We show that CYLD does not promote RIP1 deubiquitination within the membrane associated TNFR-1 complex."
24098568
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"Deubiquitination of RIP1 by CYLD triggers the disassociation of RIP1from TNFR1 and the subsequent formation of Complex II, which is comprised of FADD, RIP1, and caspase-8, leading to caspase-8 activation and apoptosis [XREF_BIBR]."
27154074
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"Inhibition of cIAP1/2 and/or deubiquitylation of RIPK1 by CYLD (not shown) induces formation of cytosolic Complex II, which consists of RIPK1, RIPK3, FADD, and pro-caspase-8 oligomers that proteolytically activate themselves."
35295146
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"These results suggest that CYLD fails to deubiquitinate RIP in the absence of optineurin."
21408173
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"Cylindromatosis tumor suppressor protein (CYLD) then deubiquitylates RIPK1 which allows this protein to leave Complex I and leads to association of FADD and RIPK3 (i.e., Complex II)."
35295146
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"Once bound to RIP1, OPTN directly interacted with cylindromatosis (CYLD) to mediate deubiquitination of RIP1 by CYLD and thereby blocked downstream of NF-κB signaling pathway (19)."
30519240
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"Indeed, knocking down CYLD with a siRNA oligo decreased the TNF-alpha plus Smac mimetic induced apoptosis, as well as caspase-8 activating complex formation, confirming that deubiquitination of RIPK1 [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18485876
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"RIPK1 is then de-ubiquitinated by the enzymes Cezanne and CYLD, and the complex of TRADD and RIPK1 moves to the cytosol as Complex II."
21981915
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"Mediating the interaction between CYLD and polyUb RIP, optineurin may act as an adaptor protein bringing CYLD and the CYLD substrate RIP together to facilitate deubiquitination of ubiquitinated RIP by CYLD."
22364875
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"In one case, A20 and CYLD both contribute to RIP1 deubiquitination, in another RIP1 deubiquitination is driven exclusively by CYLD, and in two modes either A20 or CYLD acts as the driver with the other enzyme, counterintuitively, inhibiting necroptosis."
36710493
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"Deubiquitination of RIP1 by CYLD facilitates programmed necrosis."
24098568
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"CYLD also promotes cell death through apoptosis and necrosis [XREF_BIBR, XREF_BIBR], possibly by inhibiting RIP1 ubiquitination or removing ubiquitin chains from RIP1."
23312890
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"Lys 63 linked polyubiquitination of RIP1 or TRAF2 by cIAPs results in NF-kappaB translocation into nucleus to induce transcription of its target genes including A20 and cylindromatosis (CYLD), both of which can deubiquitinate RIP1."
24938416
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"CYLD Deubiquitinates RIP1 in the TNFalpha Induced Necrosome to Facilitate Kinase Activation and Programmed Necrosis."
24098568
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"In contrast, CYLD deubiquitinates RIP1 and promotes the packaging of Complexes IIa and IIb."
26915291
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"The cellular IAP ligases (cIAP1, cIAP2) are thought to mediate RIP1 ubiquitination, and the deubiquitinating enzyme CYLD restricts RIP1 ubiquitination."
26085203
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"At the same time, RIP1 can also be deubiquitinated by CYLD, the NF-κB pathway is restricted, and the trend toward cell death pathway."
34381023
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"Subsequent work has shown that OPTN interacts with the deubiquitinase CYLD, a negative regulator of NF-kappaB that deubiquitinates RIP."
29951055
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"Another possibility is that in cells lacking normal Optn, some other protein may act as an adaptor to facilitate CYLD dependent deubiquitination of RIP."
29951055
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"32 Last but not least, CYLD interacts with and deubiquitinates RIP1."
27383048
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"This process starts with the accelerated degradation of cIAP1/2 induced by Smac protein (or Smac mimetics), and proceeds with release of RIPK1 from the TNFRI, deubiquitination of RIPK1 by the deubiqui[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
19524512
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"Conversely, deubiquitination of RIP1 by CYLD or the absence of cIAPs and LUBAC renders complex I unstable and facilitates other complexes assembled to initiate apoptosis or necroptosis."
26938298
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"Thus, apoptosis and necrosis induced by death inducing cytokines share a common biochemical pathway down to the step of RIPK1 activation following receptor activation, cIAP1/2 degradation, and deubiqu[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
19524512
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"XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR Deubiquitination of RIPK1 by CYLD 81 stimulates the dissociation of Complex I into a secondary cytoplasmic Complex IIa where RIPK1 and/or TRADD recruit FADD via their DDs."
26313917
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"CYLD, a K63 specific deubiquitinating enzyme, also mediates the deubiquitination of RIP1 to facilitate the formation of complex IIb, which is RIP1/RIP3/MLKL necrosome."
33064829
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"TNFR1 activation with no integration of c-IAPs (e.g. with the treatment of IAP antagonists), or with inhibition of translation, or with deubiquitination of RIPK1 by the deubiquitinating enzyme CYLD may induce RIPK1 translocation to a secondary complex in the cytoplasm called complex II [XREF_BIBR - XREF_BIBR]."
29587748
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"TNFR1 endocytosis, cIAP1/2 inhibition, and RIPK1 deubiquitylation by CYLD triggers formation of cytosolic Complex II, which involves dissociation of TRAF2/5 and cIAP1/2 and association of FADD and pro-caspase-8 as previously described (Newton and Manning, 2016; Su et al., 2016)."
35295146
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"RIP1 deubiquitination by CYLD promotes caspase-8 activation."
24577083
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"CYLD, a deubiquitinating enzyme that targets both M1- and K63 linked ubiquitin chains, is recruited to TNF-RSC to negatively regulate ubiquitinations of RIPK1, TNFR1, NEMO and TRADD to attenuate the NF-kappaB pathway and promote both apoptosis and necroptosis."
27984721
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"53 Finally, caspase-8 also cleaves the deubiquitylase CYLD (cylindromatosis), which is required to deubiquitylate and activate RIPK1 mediated necroptosis in response to TNF, 54 thus potentially providing an alternative or additional mechanism for silencing necroptosis."
28197335
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"Since CYLD failed to deubiquitinate RIP in the absence of optineurin, it is likely that optineurin acts as an adaptor to facilitate interaction of CYLD with RIP."
21408173
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"To test this assumption, deubiquitination of RIP by overexpressed CYLD was examined in control and optineurin knockdown cells."
21408173
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"Consistent with its role as an adaptor facilitating the association of a deubiquitinase with its substrate, depletion of optineurin impaired deubiquitination of RIP by CYLD."
21408173
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"The Lys 63 linked polyubiquitination of RIP1 or TRAF2 by cIAPs induces the translocation of NF-kappaB into the nucleus to induce the transcription of A20 and cylindromatosis (CYLD), which can both deubiquitinate RIP1."
33628745
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"As the deubiquitination of RIP1 by CYLD, a major deubiquitinase in the NF-kappaB pathway that functions by hydrolysing K63 and linear ubiquitin chains XREF_BIBR, is a key step to induce complex II formation XREF_BIBR and OPTN associates with CYLD XREF_BIBR, defects in CYLD deubiquitination activity, due to the absence of OPTN, may result in enhanced complex II formation."
27552911
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"The resulting CYLD activation would result in further deubiquitination of RIPK1 and reduction in IKK activity."
32024820
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"Optineurin directly competes with NEMO for the binding to ubiquitylated RIP and recruits CYLD, which deubiquitinates RIP to inhibit NF-kappaB activation."
29867991
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"The requirement of CYLD in forming RIPK1 dependent caspase-8 complex indicates that deubiquitination of RIPK1 by CYLD is an essential step in this process."
18485876
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"The cIAPs can ubiquitinate RIP1, which leads to activation of NF-κB and MAPK pathways to promote cell survival.39 40 Upon cIAP degradation, RIP1 can be de-ubiquitinated by deubiquitinase cylindromatosis (CYLD).41 Upon deubiquitination, Complex IIa forms (Fig. 3), which typically includes RIP1, caspase-8, and FADD.38 42 Formation of this complex can trigger cell death by apoptosis."
36157481
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"Contributing to the " death signal ", CYLD deubiquitylates TRAF2 and RIPK1, allowing the formation of the ripoptosome."
| PMC
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"As CYLD could not inhibit NF-kappaB activation in H486R expressing cells, we next examined whether CYLD can deubiquitinate RIP in presence of H486R mutant."
21408173
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"OPTN is required for CYLD dependent deubiquitination of RIP and also for CYLD dependent inhibition of TNFalpha induced by NF-kappaB activity."
29951055
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"cIAP1/2 are required for TNF induced K63 linked ubiquitination of RIP1, which functions to inhibit TNF induced apoptosis, whereas RIP1 deubiquitination by CYLD facilitates its direct interaction with caspase-8 and initiation of cell death."
21282461
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"Thus an important function of optineurin in the regulation of NF-kappaB signalling is to act as an adaptor protein bringing CYLD and its substrate RIP together to facilitate deubiquitination of ubiquitinated RIP by CYLD."
21408173