IndraLab

Statements

CYLD inhibits MAP3K7. 28 / 29
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"This is explained by loss of CYLD mediated TAK1 K63 deubiquitination [XREF_BIBR], which suppresses TAK1 activation in wild-type lymphocytes (XREF_FIG)."
23474202
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"Genetic deletion of CYLD or ITCH, essential ubiquitin regulators for TAK1 deactivation, causes strong and sustained TAK1 activation with enhanced production of tumor promoting proinflammatory cytokines that mediate liver fibrosis, tumor development, and metastasis [XREF_BIBR, XREF_BIBR]."
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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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"Additionally, in both macrophages and T cells, CYLD inhibits the ubiquitylation and subsequent activation of Tak1, a kinase that activates both IKK and JNK."
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"The fact that loss of CYLD causes spontaneous activation of TAK1 implies that TAK1 ubiquitylation is a dynamic event that occurs even in resting T cells."
18535581
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"Surprisingly, the loss of CYLD did not result in the basal activation of IKKbeta or Tak1 in macrophages."
17548520
eidos
"For instance , Ub-specific protease-14 ( USP14 ) negatively regulates the activity of proteasomes by removing Lys48-linked Ub chains , whereas cylindromatosis tumour suppressor ( CYLD ) only acts on lysine 63 linkage-specific Ub polymers.29 For example , CYLD attenuates TAK1 signalling by removing K63-linked polyubiquitin chain of TAK1 ."
30102008
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"Taken together, these findings indicated that CYLD negatively regulates the activation of TAK1, p38, and AP-1."
21931165
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"Deubiquitinating enzyme CYLD negatively regulates the ubiquitin dependent kinase Tak1 and prevents abnormal T cell responses."
17548520
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"Consistent with this result, we also found that overexpression of CYLD did not inhibit TAK1 and TAB1 co-overexpression-induced NF-kappaB activation in a reporter assay (XREF_FIG)."
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"As shown in XREF_FIG, both CYLD and IsoT effectively converted K63 polyUb chains into mono-Ub and completely blocked the activation of TAK1."
19675569
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"Specifically, CYLD positively regulates LCK in thymocytes and negatively regulates TAK1 in peripheral T cells XREF_BIBR, XREF_BIBR."
18535581
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"CYLD negatively regulates nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) signaling by removing polyubiquitin chains from specific target proteins including NF-kappaB essential modifier (NEMO), TNF receptor associated factor (TRAF) 2 and TRAF6, and Transforming growth factor beta activated kinase 1 (TAK1)."
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"Accordingly, overexpression of the deubiquitinase CYLD capable of disassembling K63 chains inhibited activation of TAK1 and NF-kappaB by VP16, whereas its catalytic mutant (CYLD-Mut) did not (XREF_FIG)."
20932476
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"Loss of CYLD causes accumulation of ubiquitinated TAK1 and aberrant TAK1 activation."
27012466
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") Moreover , Itch and Cyld act together to deactivate TAK1 through lysine 48 ( Lys48 ) - linked ubiquitination ."
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"For instance, Ub‐specific protease‐14 (USP14) negatively regulates the activity of proteasomes by removing Lys48‐linked Ub chains, whereas cylindromatosis tumour suppressor (CYLD) only acts on lysine 63 linkage‐specific Ub polymers.29 For example, CYLD attenuates TAK1 signalling by removing K63‐linked polyubiquitin chain of TAK1."
30102008
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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."
26260210
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"(41) Moreover, Itch and Cyld act together to deactivate TAK1 through lysine 48 (Lys48)-linked ubiquitination."
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"The loss of CYLD in T cells causes constitutive activation of TAK1 and its downstream signalling molecules, IKK and JNK (JUN N-terminal kinase)."
18535581
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"In keeping with a previous finding that Tak1 ubiquitination mediates its autoactivation, we have shown that CYLD potently inhibits the catalytic activity of Tak1 in transfected cells."
17548520
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"Thus, CYLD prevents excessive activation of TAK1 and p38, which results in reduced FOXP3 expression and Treg generation."
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"Deubiquitinases A20 and Cezanne, but not CYLD, are induced by NF-kappaB to negatively regulate TAK1 and NF-kappaB activity by removing K63 polyubiquitin chains [XREF_BIBR]."
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"In contrast, a catalytically inactive CYLD mutant (C601S) was unable to cleave K63 polyUb chains or inhibit TAK1."
19675569
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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."
28524749
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"CYLD inhibits Tax stimulated activation of IKK but not that of Tak1."
21824392
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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."
17548520
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"The loss of CYLD in T cells results in the constitutive activation of Tak1 and its downstream kinases JNK and IKKbeta."
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