IndraLab

Statements

CYLD is ubiquitinated. 35 / 35
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"The heightened ubiquitination and degradation of CYLD are recapitulated by hydroxylase inhibition, which suggests that post-translational hydroxylation plays a central role in E6-dependent, hypoxia-induced of CYLD degradation."
18977328
sparser
"First, co-transfection of haemagglutinin epitope tagged-MIB2 (HA-MIB2) [ xref ], CYLD (untagged) and His 6 -ubiquitin expression constructs clearly drove the ubiquitylation of CYLD compared to cells transfected with CYLD and His 6 -ubiquitin (Figure xref panel (i), compare lanes 1 and 2), suggesting that MIB2 may ubiquitylate CYLD."
25565632
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"However, the identity of the upstream E3 ubiquitin ligase responsible for ubiquitinating CYLD has remained elusive."
24961988
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"In addition to its function as a DUB, CYLD can also be ubiquitylated as a means of targeting it for proteasomal degradation."
20347313
sparser
"When serine in this region is mutated into alanine, CYLD cannot be phosphorylated, and its activity will be significantly enhanced, which will impact on CYLD ubiquitination function, resulting in the generation of apoptosis signal through NFκB signaling pathway [ xref , xref ]."
33827598
sparser
"Since optineurin knockdown cells accumulate higher levels of ubiquitinated RIP and CYLD fails to abolish NF-κB activation, it is plausible that optineurin is required for deubiquitination of RIP by CYLD."
21408173
sparser
"For these studies, we studied the state of CYLD ubiquitination in SiHa and HeLa cells that were treated with E6-specific siRNA or control siRNA."
18977328
sparser
"A proposed model explaining how p62 mutations lead to the Paget's disease of bone is the following: mutations of the UBA domain cause an impairment in the interaction between p62 and ubiquitinated TRAF6 and/or CYLD, an enzyme deubiquitinating TRAF6, which in turn enhances the activation of the NF-κB signaling pathway and the resulting increased osteoclastogenesis (Figure 3(b)) [160]."
22666256
sparser
"Hypoxia-induced degradation of CYLD is associated with E6-mediated CYLD ubiquitination."
18977328
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"CYLD binding to one of its targets, TRAF6, requires the adaptor protein p62, which promotes the deubiquitylation of TRAF6 by CYLD xref and probably also modulates the DUB activity of CYLD through induction of CYLD ubiquitylation xref ."
18535581
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"The E6-dependence of this effect is highlighted by the fact that DMOG failed to alter CYLD ubiquitination in HPV-negative cells ( xref , compare lanes 10 to 11)."
18977328
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"Hydroxylase inhibition also resulted in heightened CYLD ubiquitination and enhanced the protein-protein interaction between E6 and CYLD ( xref , compare lanes 2 to 3 and lanes 6 to 7; xref , compare lanes 2 to 3 and lanes 6 to 7; xref )."
18977328
sparser
"Here, we report that SCF β-TRCP regulates the ubiquitination and degradation of CYLD, a process dependent on prior phosphorylation of CYLD at Ser432/Ser436 by IKK."
24961988
sparser
"As expected, silencing of E6 expression (but not control siRNA) abrogated hypoxia-induced CYLD ubiquitination ( xref )."
18977328
sparser
"We have shown previously that Rig-G prevents the ubiquitination of IκBα, and CYLD, a deubiquitinating enzyme, is a direct target of miR181b-1 [ xref ]."
27602766
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"The latter observation suggested that MIB2 catalytic activity could be responsible for the ubiquitylation of CYLD."
25565632
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"How p62 mutation causes PDB is explained as follows: Mutations of the UBA domain are accompanied by impaired interaction between p62 and ubiquitinated TRAF6 and/or CYLD, a deubiquitinated enzyme for t[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
22841931
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"Co-transfection of CYLD/HA-MIB2-ΔRING/His 6 -ubiquitin prevented auto-ubiquitylation of MIB2 (Figure xref , panel (iii), compare lanes 2 and 3) and did not result in ubiquitylation of CYLD (Figure xref panel (i), compare lanes 2 and 3)."
25565632
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"In this process, downstream proteins (TAK1 and P38) were phosphorylated and activated; however, CYLD was not ubiquitinated and hydrolyzed to maintain high expression."
30894816
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"Exposure of HPV-positive cells to hypoxia led to a marked increase in ubiquitinated CYLD ( xref , compare lanes 2 to 4 and 6 to 8)."
18977328
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"SCFβ-TRCP regulates osteoclastogenesis via promoting CYLD ubiquitination."
24961988
sparser
"Our results, so far, suggest a model in which E6, in its capacity to function as part of an E3 ubiquitin ligase complex, ubiquitinates CYLD, and does so more efficiently under hypoxic conditions, thereby extinguishing the inhibitory effects of CYLD on the NF-κB pathway and leading to heightened NF-κB activation (see schematic, xref )."
18977328
sparser
"For instance, through direct or indirect effects on CYLD ubiquitination, NOTCH1 constitutively activates NF-κB signaling in CLL cells, which results in resistance to apoptosis and consequently contributes to the development and progression of CLL ( xref , xref )."
25633905
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"IKK promotes CYLD ubiquitination and subsequent degradation."
24961988
sparser
"It would be of value to determine whether (and how) CYLD phosphorylation and ubiquitylation can be reversed, or if CYLD can undergo other post-translational modifications that can prevent its phosphor[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
20347313
sparser
"The ubiquitination of CYLD can be regulated by phosphorylation, suggesting that the regulation of CYLD phosphorylation can be a potential mechanism to promote the apoptosis of hematological tumors."
33827598
sparser
"Ubiquitinated RIP and CYLD could co-immunoprecipitate along with endogenous optineurin in control cells indicating that CYLD, RIP and optineurin exist in a single complex."
21408173
sparser
"CYLD knockdown by siRNA results in constitutive ubiquitination of TRAF2. xref Constitutive ubiquitination of several other CYLD targets have also been detected in CYLD KO cells. xref , xref , xref Furthermore, CYLD mutations seem to contribute to the constitutive activation of NF- κ B in multiple myeloma cells. xref , xref Additional evidence suggests that CYLD is functionally inactivated during signal-induced NF- κ B activation."
19373246
sparser
"They found that E6, which binds E6-associated protein (an E3 ubiquitin ligase), promoted K48-linked ubiquitination of CYLD, leading to proteasomal degradation of the CYLD protein."
32883697
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"Klebsiella inhibits the activation of NFkB and MAPK pathway by promoting the expression of ubiquitinating enzyme CYLD in lung epithelial cells ( xref )."
32117248
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"For example, the adaptor protein p62, which is required for CYLD binding to TRAF6, regulates the DUB activity of CYLD by promoting CYLD ubiquitination [ xref ]."
33138315
sparser
"We then tested whether hypoxia-induced CYLD ubiquitination was dependent upon expression of E6."
18977328
sparser
"A proposed model explaining how p62 mutations lead to the Paget's disease of bone is the following: mutations of the UBA domain cause an impairment in the interaction between p62 and ubiquitinated TRAF6 and/or CYLD, an enzyme deubiquitinating TRAF6, which in turn enhances the activation of the NF- κ B signaling pathway and the resulting increased osteoclastogenesis ( xref ) [ xref ]."
22666256
sparser
"A major challenge in future studies is to show how ubiquitination of the CYLD targets regulates the NF- κ B signaling."
19373246
sparser
"These results indicate that CYLD ubiquitination is enhanced under hypoxia in an E6-dependent fashion."
18977328