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IKBKE phosphorylates CYLD. 34 / 35
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sparser
"We confirmed that CYLD is directly phosphorylated by IKKε, and that IKKε phosphorylates serine 418 in vivo ."

sparser
"More recently, IKKɛ was identified as an additional CYLD kinase — also at Ser 418 — and indeed, IKKɛ phosphorylates CYLD much more efficiently than either IKKα or IKKβ."

reach
"We next investigated if CYLD can be phosphorylated by IKKepsilon or TBK1 in the context of TCR signaling."

reach
"However, these findings suggest that the regulation of CYLD phosphorylation by IKKepsilon contributes to the NF-kappaB activity necessary for IKKepsilon mediated cell transformation."

reach
"A recent study demonstrated that IKBKE but not IKKalpha and beta phosphorylates CYLD XREF_BIBR, which is a deubiquitinase of several NF-kappaB regulators, including TRAF2, TRAF6, and NEMO, to activate the NF-kappaB pathway XREF_BIBR - XREF_BIBR."

sparser
"Since CYLD is a known tumor suppressor and IKKε is a newly-discovered oncoprotein ( xref ; xref ; xref ), we hypothesized that phosphorylation of CYLD by IKKε might play a role in the regulation of IKKε-mediated cell transformation."

sparser
"We found that transfected TBK1 and IKKε phosphorylate transfected CYLD in a 293T overexpression system, whereas the kinase-dead TBK1-K38A did not ( xref , xref )."

sparser
"We next investigated if CYLD can be phosphorylated by IKKε or TBK1 in the context of TCR signaling."

sparser
"Here we showed direct in vitro phosphorylation of CYLD by IKKε, and have used mass spectrometry and an IKKε phospho-substrate antibody to show that Ser418 of CYLD is, in fact, the in vivo site phosphorylated by IKKε."

sparser
"We show here that CYLD is a substrate of IKKε and that phosphorylation of CYLD by IKKε contributes to cell transformation."

sparser
"Phosphorylation of CYLD by IKKε promotes cell transformation by increasing NF-κB activation [ xref ], but the presence of the IKK inhibitors leads to apoptosis indicating that CYLD may be a novel therapeutic target for adult T-cell leukemia [ xref ]."

sparser
"A similar mechanism is thought to occur in breast carcinogenesis where IKKε phosphorylates and inactivates CYLD ( xref )."

sparser
"However, these findings suggest that the regulation of CYLD phosphorylation by IKKε contributes to the NF-κB activity necessary for IKKε-mediated cell transformation."

reach
"Since CYLD is a known tumor suppressor and IKKepsilon is a newly discovered oncoprotein, we hypothesized that phosphorylation of CYLD by IKKepsilon might play a role in the regulation of IKKepsilon mediated cell transformation."

sparser
"IKKɛ also phosphorylates and inactivates the tumor suppressor CYLD, preventing CYLD from deubiquitinating specific substrates in the NF-κB signaling pathway."

reach
"To examine whether TBK1 and IKKi dual inhibitors suppress CYLD phosphorylation, SCC-9 cells were treated with different TBK1 and IKKi dual inhibitors for 1 hr, and cells were collected for western blot."

sparser
"After isolating Myc immune complexes, we determined CYLD phosphorylation by IKKε pSubstrate immunoblot ( xref )."

reach
"IKKe also phosphorylates and inactivates the tumor suppressor CYLD, preventing CYLD from deubiquitinating specific substrates in the NF-kB signaling pathway."

reach
"It has been reported that phosphorylation of the tumor suppressor CYLD by IKKi promotes cell transformation 22."

sparser
"In order to determine whether IKKε can directly phosphorylate CYLD, an in vitro kinase assay was performed."

sparser
"We confirmed that CYLD is directly phosphorylated by IKKepsilon and that IKKepsilon phosphorylates serine 418 in vivo."

reach
"For example, IKBKE phosphorylates CYLD and TRAF2 in breast cancer cells, which induces NF-κB activation and contributes to cell transformation [35, 36]."

reach
"We show here that CYLD is a substrate of IKKepsilon and that phosphorylation of CYLD by IKKepsilon contributes to cell transformation."

sparser
"Hutti et al. have reported that IKKε could also phosphorylate CYLD to inhibit its activity xref ."

sparser
"It has been reported that phosphorylation of the tumor suppressor CYLD by IKKi promotes cell transformation xref ."

sparser
"CYLD, a NF-κB inhibitor acting as a tumour suppressor, is phosphorylated by IKKε, a modification that decreases its deubiquitine ligase activity and consequently its inhibitory potential [ xref ]."

sparser
"This mechanism of CYLD inactivation has been subverted by the breast cancer oncogene IKKε, which phosphorylates CYLD and inactivates its DUB function [ xref ]."

reach
"The TCR- and PMA/I induced Ser418 phosphorylation of CYLD could be completely prevented by dual inhibition of IKKepsilon and TBK1, using MRT67307, while the IKKbeta inhibitor TPCA1 had no effect."

sparser
"IKKe also phosphorylates and inactivates the tumor suppressor CYLD, preventing CYLD from deubiquitinating specific substrates in the NF-kB signaling pathway."

reach
"More recently, IKKepsilon was identified as an additional CYLD kinase -- also at Ser 418 [50] -- and indeed, IKKepsilon phosphorylates CYLD much more efficiently than either IKKalpha or IKKbeta."

reach
"CYLD phosphorylation can be pharmacologically reversed by IKK inhibitors, specifically by TBK1/IKKepsilon and IKKbeta inhibitors (MRT67307 and TPCA)."

rlimsp
"Phosphorylation of the tumor suppressor CYLD by the breast cancer oncogene IKKepsilon promotes cell transformation."

sparser
"Hutti et al. [ xref ] showed that IKKε phosphorylates the tumor suppressor CYLD (Ser418) to suppress its deubiquitinase activity and to promote oncogenesis."

sparser
"Intrigued by the faster inactivation of CYLD in P1 and P2 ( xref ), we probed the possibility that TBK1 and IKKε phosphorylate CYLD ( xref ; xref ), and assessed the contribution of that interaction to RCD."