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CYLD inhibits IKK_complex. 44 / 45
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"Taken together with the hyperphosphorylation of IκBα ( Figure 5 ), these findings suggested that the Cyld deficiency caused spontaneous activation of the IKK."
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"Since the constitutive ubiquitination of RIP1 in Cyld −/− testicular cells was associated with IKK activation, we examined whether the Cyld deficiency caused constitutive association of IKKγ with RIP1[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Together, these results suggest that loss of CYLD results in uncontrolled ubiquitination of RIP1, which in turn recruits and activates IKK, leading to deregulated NF-κB activation and aberrant express[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"CYLD negatively regulates the activation of IKK and JNK, and its expression is markedly upregulated under conditions of RANKL induced osteoclastogenesis [XREF_BIBR]."
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"However, despite its essential role in spontaneous activation of TAK1 in T cells, the loss of CYLD in Jurkat T cells did not appreciably prolong the IKK activation induced by TNFalpha."
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"Overexpression of the deubiquitination enzymes CYLD and A20, which are known to inhibit NF-κB, reduced the numbers of NEMO condensates and inhibited IKK activation in U2OS cells stimulated with IL-1β or TNFα (Figure 4E and S8), indicating that polyUb chains are required for the formation of NEMO condensates."
35477005
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"Conversely, the overexpression of two DUBs, CYLD and A20, which are well-known inhibitors of NF-κB, significantly reduces NEMO condensation and inhibits IKK activation [100]."
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"The loss of CYLD in both primary T cells and the Jurkat T cell line causes the constitutive activation of Tak1 as well as its downstream targets JNK and IKK."
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"These include the deubiquitination enzymes CYLD and A20 that inhibit IKK, and the ubiquitin binding proteins NEMO and TAB2 which are the regulatory subunits of IKK and TAK1 kinase complexes, respectively."
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"CYLD may prevent excessive inflammation due to an antiviral innate immune response by suppressing IKK complex and NF-κB activation downstream of TLR3 in hRPTECs."
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"We further demonstrate that CYLD also negatively regulates IkappaB kinase, although this function of CYLD is seen in a receptor dependent manner."
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"These observations suggest that suppression of CYLD enhances the activity of the IKK kinase and the nuclear localization of NF-kappaB transcription factors."
20832754
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"The NF-kappaB signaling pathway is a key regulator of inflammatory responses and CYLD may negatively regulate IKK complex activation to inhibit the NF-kappaB signaling pathway via deubiquitinating IKKgamma."
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"Furthermore, addition of viral OTU (vOTU) WT but not the mutant C40A, or CYLD WT but not the mutant C601A, also blocked IKK activation by Tax (XREF_FIG)."
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"On the other hand, overexpression of two DUBs, CYLD and A20, the well-known inhibitor of NF-κB, significantly reduces the number of NEMO puncta and inhibits the IKK activation."
37294105
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"In doing so, CYLD inhibits IKK activation by agents such as TNFalpha, IL-1beta and phorbol ester (PMA)."
15196553
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"Conversely, loss of the K63 specific deubiquitinase CYLD causes spontaneous activation of IKK and JNK as well as their upstream kinase Tak1."
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"CYLD deletion causes accumulation of constitutively active TAK1, and its downstream kinases JNK and IKK, which results in T cells that become hyper-responsive to TCR stimulation."
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"CYLD and A20 function as deubiquitination enzymes to inhibit IKK by targeting RIP1 upstream of IKK, while CUEDC2 acts as an adaptor protein to keep IKK in an inactivated status by recruiting a phospha[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"161 Cylindromatosis (CYLD) has been shown to inhibit NFkappaB activation 160 and more recent results indicate that this inhibition might be mediated via the ability of CYLD to hydrolyze unanchored polyubiquitin chains and thus inhibit TAK1 and IKK activation."
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"CYLD inhibits IKK by cleaving K63 linked polyubiquitin chains on TRAF2, TRAF6 and NEMO XREF_BIBR, XREF_BIBR Interestingly, in patients with the cylindromas (a type of tumor), a mutation in the DUB domains of CYLD has been reported, suggesting its role of tumorgenesis 19."
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"CYLD also negatively regulates the IKK related kinases, IKKepsilon and TBK1, by the same mechanisms."
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"The de-ubiquitylating enzyme CYLD (cylindromatosis tumor suppressor protein) can impair IKK activation by cleaving the Lys63-linked ubiquitin chain on several proteins comprising TRAF6 and NEMO, exemp[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Despite its essential role in suppressing the constitutive activity of IKKbeta in T cells, the loss of CYLD in Jurkat T cells did not appreciably prolong the IKK activation induced by TNF-alpha or mitogens."
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"Likewise, the tumour suppressor cylindromatosis protein, CYLD, which functions as a deubiquitinating enzyme and downregulates TRAF-dependent IKK activation [26] , also failed to block parasite-induced[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Loss of CYLD in T cells leads to constitutive activation of TAK1 and its downstream kinases c-Jun N -terminal kinase (JNK) and IκB kinase β (IKKβ)."
31078284
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"CYLD inhibited the activity of the IKK complex by removing the K63 ubiquitin chains on NEMO, the regulatory subunit of the IKK complex."
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"CYLD inhibits IKK by cleaving K63-linked polyubiquitin chains on TRAF2, TRAF6 and NEMO xref , xref Interestingly, in patients with the cylindromas (a type of tumor), a mutation in the DUB domains of CYLD has been reported, suggesting its role of tumorgenesis xref ."
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"CYLD, on the other hand, degrades the polyubiquitinated chain of K63 on TRAF2/6 and IKK when it acts as a deubiquitinating enzyme to lead to the breakdown of the IKK complex, and finally inhibits the activation of NF-κB as a negative feedback, thus providing an apoptotic environment [19]."
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"CYLD suppresses the activation of IKK complex by cleaving K63-linked polyubiquitin chains from TAK1 [42] and linear ubiquitin chains from NEMO [43]."
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"In mature T cells, CYLD targets TAK1 for inactivation to downregulate IKK and NF-kappaB activation [XREF_BIBR]."
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"One of these DUBs is the cylindromatosis tumor suppressor protein, CYLD, which inhibits IKK activation by cleaving K63-linked poly-ubiquitin chains on several proteins, including TRAF2, TRAF6 and NEMO."
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"Notch is capable of enhancing NF-kappaB activity by a Hes1 dependent mechanism (Hes1 mediated suppression of Cyld, a deubiquitinase that negatively regulates the IKK complex) 53 and Hes1 independent mechanisms (NICD induced expression of NF-kappaB, NICD enhanced IKKalpha activity, or NICD mediated NF-kappaB nuclear retention) XREF_BIBR - XREF_BIBR."
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"Further support to this model came from the discoveries by other laboratories that CYLD and A20 function as deubiquitination enzymes to inhibit IKK (reviewed by V. Dixit)."
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"These include IkappaBalpha re-synthesis with consequent export of RelA containing dimers to the nucleus, ubiquitin mediated RelA proteasomal degradation triggered by its phosphorylation by IKKalpha and implemented by SOCS1 and COMMD1 or PDLIM2 proteins, RelA displacement from DNA by PIAS proteins, and inactivation of the IKK complex or its upstream regulators by the A20 and CYLD deubiquitinating enzymes."
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"CYLD inhibits Tax stimulated activation of IKK but not that of Tak1."
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"Overexpression of CYLD inhibits IKK activation, whereas reducing CYLD expression has the opposite effect XREF_BIBR, XREF_BIBR, XREF_BIBR."
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"CYLD was shown to inactivate TRAF2, TRAF6, and IKKγ by removing the K63-linked polyubiquitin chains ( Kovalenko et al., 2003 ), whereas A20 removes K63-linked polyubiquitin chains from TRAF2, TRAF6, a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Hes1, which is downstream of Notch signalling, can inhibit the transcription of the deubiquitinase CYLD, which negatively regulates IKK [44]."
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"We also overexpressed in HEK293 cells the deubiquitinase CYLD, which can remove ubiquitin chains with linear as well as KLys-63 linkages (XREF_FIG D) and which inhibited full IKK activation by TNF-alpha (XREF_FIG E)."
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"Cyld -deficient mice have been generated by different groups, and these mice display a myriad of phenotypes that overall support the conclusion that CYLD inhibits IKK and NF-kappaB and contributes, at[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"CYLD is known to inhibit IKK and NF-kB signalling through deubiquitination of TRAF2, TRAF6 and NEMO and is involved in neuronal death and its ablation is protective for trauma-induced brain damage."
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"Importantly, expression of wildtype CYLD, but not its catalytically inactive mutant, strongly inhibited Tax stimulated activation of IKK, supporting a role for Tax ubiquitination in the activation of IKK signaling."
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"In T cell acute lymphoblastic leukemia (T-ALL), CYLD expression is repressed by the Notch and Hes1 pathway to promote persistent IKK activation and cell survival [XREF_BIBR]."
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