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IKK_complex phosphorylates CYLD. 43 / 43
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sparser
"IKK family kinases phosphorylate CYLD in the ATLL MT4 cell line."

sparser
"Additionally, in primary adult T-cell leukemia/lymphoma (ATLL) samples and cell lines, increased IKK-induced CYLD phosphorylation was observed."

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

reach
"To examine if IKK directly phosphorylates CYLD, 0.25 mug of purified CYLD was incubated with purified IKKbeta, at a final concentration of 15 nM, in medium containing 1mM EGTA, 5 mM MgCl 2, 50 mug/uL leupeptin, 2.5 mM DTT, 1 mg/mL BSA, 6.5% glycerol, in 20 mM HEPES, pH 7.4, with or without 100 muM ATP in a final volume of 20 muL at 37degreesC for one hour."

reach
"Interestingly, TBK1 or IKKε specifically causes CYLD to shift to higher molecular bands, suggesting phosphorylation of CYLD by these kinases."

sparser
"These results suggest that IKK phosphorylates CYLD at the PSD under basal condition."

reach
"These results suggest that IKK phosphorylates CYLD at the PSD under basal condition."

reach
"CYLD interacts with NEMO and is phosphorylated by IKK as a mechanism to inactivate CYLD DUB activity."

sparser
"Therefore, IKK phosphorylates CYLD to inactivate its DUB function thus providing a window of NF-κB activation prior to signal-induced termination by A20."

reach
"Phosphorylation of the tumor suppressor CYLD by the breast cancer oncogene IKK."

sparser
"The second possibility tested was phosphorylation of CYLD by IKK."

rlimsp
"As IKK-mediated phosphorylation of CYLD has been reported to negatively regulate CYLD enzymatic activity [34], we further explored whether IKK is also involved in regulating the degradation of CYLD by SCFβ-TRCP."

sparser
"Reiley et al have shown that NEMO is required for the IKK complex to phosphorylate and inhibit the deubiquitinase CYLD [ xref ], a critical component of the necrotic machinery [ xref ], as can the TNF-inducible IKKε [ xref ]."

rlimsp
"Although this identified phospho-degron motif (GSIGHS) within CYLD is not consistent with the canonical β-TRCP degron (DSGXXS), it does resemble a reported non-canonical degron found within p53 that also contains IKK phosphorylation sites, and other known β-TRCP substrates including Mcl-1, PHLPP1 and Gli2 (Supplementary Figure 3A) [35-38]."

reach
"To investigate further if IKK kinases are involved in phosphorylating CYLD in MT4 cells, we examined the effect of MRT67307 (TBK1/IKKɛ inhibitor) and TPCA (IKKβ inhibitor)."

reach
"IKK, a Ca 2+ -independent kinase, known to phosphorylate CYLD at S-418 in non neuronal cells [XREF_BIBR], [XREF_BIBR], is present in the PSD fractions [XREF_BIBR]."

reach
"39 Interestingly, the phosphorylation of CYLD is mediated by IKK, 39 implying that CYLD may not be a major factor involved in feedback control of NF-kappaB activation."

reach
"The following are some well-known and extensively studied examples.Phosphorylation of CYLD by IKKε promotes cell transformation by increasing NF-κB activation [104], but the presence of the IKK inhibitors leads to apoptosis indicating that CYLD may be a novel therapeutic target for adult T-cell leukemia [31]."

sparser
"Phosphorylation of the tumor suppressor CYLD by the breast cancer oncogene IKK. promotes cell transformation."

reach
"However, constitutive phosphorylation of CYLD by IKK inactivates CYLD in HTLV-1-induced leukemia to promote heightened NF-kappaB activation."

reach
"IkappaB kinase (IKK), with regulatory subunit IKKgamma, phosphorylates CYLD and results in the loss of its deubiquitinating function towards TRAF2."

sparser
"Interestingly, phosphorylation of CYLD by IKK inhibits its DUB activity ( xref )."

reach
"Activation of IKK in isolated PSDs also promoted phosphorylation of CYLD and an increase in endogenous deubiquitinase activity for K63 linked polyubiquitins."

reach
"Regarding the latter possibility, a recent study suggests that CYLD phosphorylation can also be mediated by the IKK related kinase IKKepsilon and contributes to IKKepsilon induced tumorigenesis [XREF_BIBR]."

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

sparser
"Addition of ATP induced phosphorylation of CYLD at S-418 ( xref ), indicating that IKK can directly phosphorylate CYLD."

sparser
"However, constitutive phosphorylation of CYLD by IKK inactivates CYLD in HTLV-1-induced leukemia to promote heightened NF-κB activation ( xref )."

reach
"IkappaB kinase (IKK), with regulatory subunit IKKgamma, phosphorylates CYLD and results in the loss of its deubiquitinating function towards TRAF2."

sparser
"Furthermore, the IKK complex that phosphorylates CYLD is also necessary for the induction of NF-κB-dependent transcription."

reach
"In HTLV-1 infected cells CYLD is constitutively phosphorylated by IKK, which impairs its function thus allowing persistent NF-kappaB activation [XREF_BIBR, XREF_BIBR]."

sparser
"CYLD interacts with NEMO and is phosphorylated by IKK as a mechanism to inactivate CYLD DUB activity ( xref )."

sparser
"We now report that phosphorylation of CYLD by IKK family kinases in HTLV-1 transformed T cells inhibits RIPK1 from activating the cell death pathway and inhibiting these kinases reactivates CYLD and RIPK1-dependent tumor cell death."

reach
"Therefore, in order to determine which IKK family member (s) can most efficiently phosphorylate CYLD, we cotransfected Myc-CYLD with individual IKK family members fused to GST."

reach
"Addition of ATP induced phosphorylation of CYLD at S-418 (XREF_FIG), indicating that IKK can directly phosphorylate CYLD."

sparser
"In HTLV-1 infected cells CYLD is constitutively phosphorylated by IKK, which impairs its function thus allowing persistent NF-κB activation [ xref , xref ]."

reach
"Activation of IKK in isolated PSDs also promoted phosphorylation of CYLD and an increase in endogenous deubiquitinase activity specific for K63 linked polyubiquitins."

sparser
"To ensure that IKK could directly phosphorylate CYLD rather than via sequential phosphorylation through other PSD-associated kinases, purified CYLD and purified IKKβ (catalytic subunit) were co-incubated in the presence or the absence of ATP."

reach
"The second possibility tested was phosphorylation of CYLD by IKK."

reach
"Seminal work by Sun and colleagues showed that CYLD was phosphorylated by IKKβ and this inhibited its catalytic activity ."

reach
"Both of the IKK sub-families can phosphorylate CYLD, and the combination of MRT67307 and TPCA have a marked effect in reducing CYLD phosphorylation and triggering cell death."

reach
"To ensure that IKK could directly phosphorylate CYLD rather than via sequential phosphorylation through other PSD associated kinases, purified CYLD and purified IKKbeta (catalytic subunit) were co-incubated in the presence or the absence of ATP."

reach
"These observations indicate that endogenous IKK activity in isolated PSDs mediates CYLD phosphorylation in the absence of Ca 2+."

reach
"Interestingly, the CYLD phosphorylation requires IkappaB kinase gamma (IKKgamma) and can be induced by IKK catalytic subunits."