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CYLD is phosphorylated on S418. 59 / 59
| 53 6
sparser
"The TCR- and PMA/I-induced Ser418 phosphorylation of CYLD could be completely prevented by dual inhibition of IKKε and TBK1, using MRT67307, while the IKKβ inhibitor TPCA1 had no effect (Figure xref )."
29755980
sparser
"To further elucidate the importance of CYLD phosphorylation at Ser418 for proximal TCR signal transduction, we generated CYLD knockout cells by CRISPR/Cas9 to subsequently reconstitute with CYLD(S418A) or CYLD(S418E) mutants that prevent or mimic CYLD phosphorylation at Ser418, respectively."
29755980
sparser
"Application of either inhibitor reduced CYLD phosphorylation at S-418 in a dose-dependent manner ( xref )."
24928390
sparser
"We focused on CYLD phosphorylation at Ser418, which can be easily assessed using a phospho(Ser418)-CYLD-specific antibody."
29755980
sparser
"Phosphorylation of CYLD at serine 418 decreases its deubiquitinase activity and is necessary for IKKε-driven transformation."
19481526
sparser
"Phosphorylation of CYLD at Ser418 decreases CYLD activity."
19481526
sparser
"Further examination showed that phosphorylation of CYLD at S418 decreases its deubiquitinase activity and increases NF-κB activation."
19481526
rlimsp
"However, in the PSD fraction, CaMKII inhibitor CN21 could not completely block the phosphorylation of CYLD at S-418, implicating involvement of a second kinase in its phosphorylation (Fig."
24614225
sparser
"Together, these observations indicate that, in addition to CaMKII, a Ca 2+ -independent kinase at the PSD phosphorylates CYLD at S-418."
24614225
sparser
"These results demonstrate that phosphorylation of CYLD at Ser418 suppresses CYLD activity, resulting in increased NF-κB transcriptional activation."
19481526
sparser
"Indeed, CYLD could be readily detected upon immunoprecipitation with the phospho(Ser418)-CYLD-specific antibody from PMA/I-stimulated Jurkat T cells and primary murine CD4 + T cells, showing that CYLD is indeed phosphorylated at Ser418 upon T cell stimulation but that its direct detection with the phospho(Ser418)-CYLD-specific antibody in a western blot is masked by another inducible protein of the same size that is recognized by the same antibody."
29755980
sparser
"For example, phosphorylation of CYLD (cylindromatosis, or turban tumor syndrome) on S418 decreases the rate in processing polyubiquitinated TRAF2 and NEMO (also known as IKK-γ; xref ; xref ; xref )."
25904330
sparser
"In this model, the downregulated phosphorylation of serine 418 of CYLD enhances the recruitment of RIPK1 to complex 2 by removing the K63-linked polyubiquitin chains of RIPK1, which promotes cell death [ xref ]."
33919439
sparser
"CYLD is a deubiquitinase that affects NFKappaB signaling through regulation of the ubiquitin state of its targets, including TRAF6 and TRAF2. xref Phosphorylation of CYLD at S418 has been shown to reduce its deubiquitinase activity, leading to increased NFkappaB signaling. xref "
30114907
sparser
"Together, these observations demonstrate that IKKε-mediated phosphorylation of CYLD at Ser418 inhibits CYLD deubiquitinase activity."
19481526
rlimsp
"However, the phospho(Ser418)-CYLD immunoreactive band was still present in CRISPR/Cas9 generated IKKε/TBK1 double knockout cell lines, where it could still be prevented by MRT67307, indicating that the initially observed inhibitory effect of MRT67307 on TCR-induced CYLD phosphorylation is IKKε/TBK1-independent."
29755980
sparser
"In TNFR1 signaling, IKK-mediated phosphorylation at serine 418 of CYLD protects cancer cells against cell death by downregulating CYLD activity [ xref , xref , xref ]."
33919439
sparser
"While it is therefore possible for any of these IKK family members to phosphorylate Ser418 of CYLD, CYLD is a much better substrate for IKKε than for IKKα or IKKβ."
19481526
sparser
"We set out to analyze if the noncanonical kinases IKKε and TBK1 regulate TCR-mediated signaling by phosphorylating the deubiquitinase CYLD at Ser418 in Jurkat T cells."
29755980
sparser
"From Figure xref it is obvious that this antibody specifically recognizes CYLD phosphorylation at Ser418 upon overexpression."
29755980
rlimsp
"Mass spectrometric analysis on the recombinant CYLD incubated with PSD fractions showed that addition of ATP can induce phosphorylation at S-418, even in the absence of Ca2+, a result confirmed by Western immunoblotting experiments with an antibody specific for phospho CYLD (S-418) (Fig."
24614225
sparser
"Interestingly, immunoprecipitation with the phospho(Ser418)-CYLD antibody, followed by immunoblotting with anti-CYLD, revealed that CYLD is phosphorylated by IKKε/TBK1 at Ser418 upon T cell stimulation, but that its direct detection with the phospho(Ser418)-CYLD-specific antibody in a western blot is masked by another inducible protein of the same size that is recognized by the same antibody."
29755980
sparser
"Phosphorylation of Ser418 of CYLD inhibits CYLD-mediated TRAF2 deubiquitination, promoting TNF-induced gene expression ( xref ; xref )."
34966378
rlimsp
"Consistent with mass-spectrometric results, Western immunoblots using an antibody specific for phospho CYLD (S-418) showed that purified CaMKII phosphorylates purified CYLD on this residue (Fig."
24614225
sparser
"More specifically, we focused on CYLD phosphorylation at Ser418, which can be detected upon immunoblotting of cell extracts with phospho(Ser418)-CYLD specific antibodies."
29755980
sparser
"For instance, phosphorylation of CYLD at Ser418 or USP7 at Ser18 led to an increase in the activities of these two DUBs."
27597804
sparser
"Overexpression of IKKε alone is sufficient to drive transformation of NIH-3T3 cells by phosphorylating CYLD at Ser418 and decreasing its deubiquitinase activity [ xref ]."
30791439
sparser
"Upon finding that an oncoprotein is capable of strongly phosphorylating a known tumor suppressor, we predicted that CYLD phosphorylation at Ser418 might play an important role in cell transformation."
19481526
sparser
"Consistent with an earlier report xref , western blotting with an antibody that detects phosphorylation of CYLD at serine 418 showed this posttranslational modification to be elevated in the HTLV-1-transformed cell lines (Fig. xref )."
32024820
sparser
"When the two proteins were incubated in the presence of ATP, CYLD became phosphorylated at S-418 and the rate of degradation of added K63-linked Ub4 increased ( xref )."
24928390
sparser
"In addition, ubiquitin carboxyl-terminal hydrolase CYLD (CYLD) phosphorylated at serine 418 and either serine 422 or threonine 424 was significantly increased at 24 h."
30114907
sparser
"This analysis confirmed that CYLD is phosphorylated at Ser418, the same site predicted by our bioinformatic analysis ( xref )."
19481526
sparser
"Together these data suggest that T cell activation is associated with the IKKε/TBK1 mediated phosphorylation of CYLD at Ser418."
29755980
sparser
"Phosphorylation of CYLD at Ser418 was detected upon immunoblotting of cell extracts using phospho(Ser418)-CYLD-specific antibodies."
29755980
sparser
"At the posttranslational level, the IKK complex has been shown to mediate phosphorylation at serine 418 of CYLD (although this remains controversial ( xref )), downmodulating its deubiquitinase activity following treatment with TNF-α ( xref )."
32883697
sparser
"Phosphorylation of Ser418 of CYLD inhibits CYLD-mediated TRAF2 deubiquitination, promoting TNF-induced gene expression (Reiley et al., 2005; Hutti et al., 2009)."
34966378
sparser
"Experiments with an antibody specific to CYLD phosphorylated at S-418 (p-CYLD) show that incubation of PSD fractions in the presence of ATP in EGTA-containing medium induces phosphorylation of CYLD ( xref , top panels), confirming previous results by mass spectrometry [ xref ]."
24928390
sparser
"There is some initial evidence that IKKγ (I kappa B kinase gamma) mediates CYLD phosphorylation on Ser 418 [ xref ], although a more recent report suggests that IKKε (I kappa B kinase epsilon) is a much more efficient kinase for this site [ xref ]."
21480003
sparser
"Recently, this was further confirmed by demonstrating the requirement of IKKɛ-mediated phosphorylation at Ser418 of the tumor suppressor CYLD, which prevents its deubiquitinating activity on NF-κB signaling proteins such as TRAF2 and NEMO xref , xref ( xref )."
23333767
sparser
"Phosphorylation of CYLD at serine 418 decreases its deubiquitinase activity and is necessary for IKKepsilon-driven transformation."
19481526
rlimsp
"Phosphorylation of CYLD at serine 418 decreases its deubiquitinase activity and is necessary for IKKepsilon-driven transformation."
19481526
sparser
"Similarly, CYLD Ser418 phosphorylation upon co-expression of IKKε was found to decrease its DUB activity (Hutti et al., xref )."
29755980
sparser
"Remarkably, there is also a contradictory report showing that CYLD Ser418 phosphorylation increases its in vitro DUB activity toward K63-linked polyubiquitin (Thein et al., xref )."
29755980
sparser
"Moreover, IKKε, a noncanonical IKK family member, phosphorylates CYLD at serine 418 and reduces its deubiquitinase activity, leading to induction of oncogenic transformation [ xref ]."
27844253
sparser
"In agreement with observations using purified proteins, inclusion of IKK inhibitor attenuated phosphorylation of CYLD on S-418 as well as the degradation of K63-linked polyubiquitins in the PSD fractions ( xref )."
24928390
sparser
"Together, these data confirm that CYLD Ser418 is phosphorylated in vivo in the presence of IKKε."
19481526
sparser
"Another NF-κB inhibitory DUB, OTULIN inhibits Ser418 phosphorylation of CYLD through a LUBAC-dependent mechanism, which sustains its catalytic activity, while hyperphosphorylation of OUTLIN at Tyr56 regulates necroptosis by modulating RIPK1 ubiquitin dynamics [ xref ]."
32512887
sparser
"Stimulation of Jurkat T cells with anti-CD3/CD28 or PMA/I led to the rapid phosphorylation of CYLD at Ser418 (Figure xref )."
29755980
rlimsp
"More specifically, we focused on CYLD phosphorylation at Ser418, which can be detected upon immunoblotting of cell extracts with phospho(Ser418)-CYLD specific antibodies."
29755980
sparser
"Following stimulation, CYLD undergoes phosphorylation at serine-418 and serine-568 residues catalyzed by either canonical IKKs (IKKα and IKKβ) or by the noncanonical IKKε, which may increase DUB activity of CYLD."
35109788
sparser
"IKK, a Ca 2+ -independent kinase, known to phosphorylate CYLD at S-418 in non-neuronal cells [ xref ], [ xref ], is present in the PSD fractions [ xref ]."
24928390
sparser
"Recently, this was further confirmed by demonstrating the requirement of IKKe-mediated phosphorylation at Ser418 of the tumor suppressor CYLD, which prevents its deubiquitinating activity on NF-kB signaling proteins such as TRAF2 and NEMO [41, 71] (Fig. 3) ."
23333767
sparser
"Addition of ATP induced phosphorylation of CYLD at S-418 ( xref ), indicating that IKK can directly phosphorylate CYLD."
24928390
sparser
"CYLD Ser418 phosphorylation was also observed upon co-expression with IKKε or TBK1, but not upon co-expression of their catalytically inactive counterparts (K38A) in HEK 293T cells (Figure xref )."
29755980
sparser
"However, in the PSD fraction, CaMKII inhibitor CN21 could not completely block the phosphorylation of CYLD at S-418, implicating involvement of a second kinase in its phosphorylation ( xref - right)."
24614225
sparser
"Recently, this was further confirmed by demonstrating the requirement of IKKɛ-mediated phosphorylation at Ser418 of the tumor suppressor CYLD, which prevents its deubiquitinating activity on NF-κB signaling proteins such as TRAF2 and NEMO [41], [71] (Fig. 3)."
23333767
sparser
"Immuno electronmicroscopy on hippocampal cultures, using an antibody for CYLD phosphorylated at S-418, revealed that the phosphorylated form of CYLD is present at the PSD under basal conditions."
24928390
sparser
"Enhanced RIPK1 recruitment to Complex II in Sharpin cpdm/cpdm cells correlated with impaired phosphorylation of CYLD at serine 418, a modification reported to inhibit its enzymatic activity."
34887354
sparser
"IKKε-mediated phosphorylation of CYLD at S418 facilitates transformation."
19481526