IndraLab

Statements

CYLD affects TRAF2
2 7 1 1 | 69 30
CYLD binds TRAF2.
7 1 | 16 26
TRAF2 binds CYLD. 10 / 42
7 1 | 14 18
reach
"A point mutation in CYLD that abolishes CYLD binding to TRAF2 greatly increases polyubiquitin-TRAF2 levels."
15571815
sparser
"Surprisingly, however, CYLDex7/8 mutant HSCs did not significantly activate the NF-κB pathway, but instead p38MAPK signaling, indicating that CYLD–TRAF2 interactions elicit a signaling cascade that is HSC specific."
25824820
sparser
"Lacking of exons 7 and 8 of Cyld (Cyld ex7/8 ) abrogates the interaction of CYLD-NEMO and CYLD-TRAF2 ( xref )."
38562929
reach
"Notably, CYLD physically interacts with and deubiquitinates TRAF2, an E3 ubiquitin–protein ligase that modifies itself with Lys63-linked ubiquitin chains."
15571815
sparser
"CYLD interacts directly with TRAF2, an adaptor molecule involved in signaling by members of the family of TNF/nerve growth factor receptors ( xref , xref )."
19489724
reach
"Mechanistically, CYLD binds to NEMO and TRAF2 and reverses non-K48-linked polyubiquitination of TRAF2, thereby blocking TRAF2 mediated activation of the IKK complex [XREF_BIBR - XREF_BIBR] (XREF_FIG)."
27844253
sparser
"CYLD also binds the TNF receptor–associated factor 2, which is an upstream activator of IKK."
15100680
sparser
"Our study adds a novel level of complexity to this scenario, revealing that the interaction between the DUB CYLD and the adaptor protein, E3 ubiquitin ligase TRAF2, elicits a signaling pathway that promotes dormancy and thus prevents HSCs from unscheduled proliferation and exhaustion."
25824820
sparser
"Although our CYLDex7/8 mouse model indicates that the TRAF2-binding domain is crucial to control HSC function by promoting the interaction between CYLD and TRAF2, we cannot formally exclude that unknown substrates bind to this domain as well."
25824820
reach
"Interestingly, CYLD interacts with NEMO and TRAF2, both of which are recruited to the TNF receptor upon ligand binding."
14676304
CYLD binds IKBKG and TRAF2. 3 / 3
| 3
sparser
"The direct interaction of CYLD with both TRAF2 and NEMO is facilitated by N-terminal protein-protein interaction domains and contributes to its activity toward these substrates ( Kovalenko et al., 200[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18313383
sparser
"Mechanistically, CYLD binds to NEMO and TRAF2 and reverses non-K48-linked polyubiquitination of TRAF2, thereby blocking TRAF2-mediated activation of the IKK complex [ xref - xref ] ( xref )."
27844253
sparser
"Interestingly, CYLD interacts with NEMO (IKKγ; references xref – xref ) and TRAF2 ( xref , xref ), both of which are recruited to the TNF receptor upon ligand binding."
14676304
RIPK1 binds TRAF2 and CYLD. 2 / 2
| 2
sparser
"TNFα treatment increases the binding between PrP and the deubiquitinase tumor suppressor cylindromatosis (CYLD), in these treated cells, binding of CYLD to RIP1 and TRAF2 is reduced."
28900035
sparser
"Interactions between CYLD and RIP1 or TRAF2 were specific as isotype controls did not pull down any CYLD ( xref , A and B )."
28900035
CYLD binds TRAF2 and K63. 1 / 1
| 1
reach
"When CYLD associates with TRAF2, it removes the K63 and M1 poly-ubiquitin chains from RIPK1, thereby allowing RIPK1 to dissociate from the TNFR1 complex."
33324405
TRAF2 binds IKBKG, BCL3, and CYLD. 1 / 1
| 1
sparser
"In addition to these well-defined protein domains, new domains of CYLD have been defined, based on mutational analyses, for the interaction of CYLD with TRAF2, IKKγ and BCL-3 (Refs xref , xref )."
18535581
TNFAIP3 binds CYLD, TNFRSF9, and TRAF2. 1 / 1
| 1
sparser
"The deubiquitinases A20 and CYLD interact with the 4-1BB and TRAF2 complex and, by regulating the ubiquitination of TRAF2 and TAK1 ( xref ), they decrease 4-1BB activation [ xref ]."
| PMC
IKK_complex binds TRAF2, TRAF6, and CYLD. 1 / 1
| 1
sparser
"The initial clue to the signaling function of CYLD came from an RNAi-based functional screening study, which identified CYLD as a DUB that negatively regulates NF- κ B activation. xref At the same time, yeast two-hybrid screening studies identified CYLD as a protein that binds to NF- κ B essential modulator (NEMO), a regulatory subunit of I κ B kinase (IKK). xref , xref CoIP assays also revealed the association of CYLD with two IKK regulatory proteins, TRAF2 and TRAF6, and subsequent studies identified additional molecular targets of CYLD ( xref )."
19373246
TRAF2 binds mutated CYLD. 1 / 1
| 1
reach
"The biochemical analysis using phosphomimetic mutants demonstrated that this PTM negatively affects the deubiquitinating activity of CYLD on TRAF2, most likely through interfering with the catalytic activity of CYLD, since the binding of TRAF2 to a CYLD mutant mimicking phosphorylation on Ser 418 is not affected."
21480003
CYLD deubiquitinates TRAF2.
1 1 | 31
CYLD deubiquitinates TRAF2. 10 / 30
1 1 | 28
reach
"Another example is already mentioned CYLD, which is an important inflammatory mediator that deubiquitinates TRAF2 and TRAF6, resulting in negative regulation of the NF-kappaB pathway [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR]."
23151130
reach
"CYLD deubiquitinates TRAF2, TRAF6 and NEMO, and inactivation of CYLD increases NF-ĸB signaling in a sustained manner, both in vitro and in vivo [43]."
39334439
reach
"CYLD, a protease that specifically cleaves K63-ubiquitin chains, de-ubiquitinates TRAF2, thereby inhibiting the recruitment of TAB and TAK and activation of IKK [15], and A20 deactivates RIP1 by remov[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24746195
reach
"A series of recent reports have shown that CYLD blocks signal transmission through the classical NF-κB cascade by deubiquitinating the TNF receptor-associated factor 2 (TRAF2), TRAF6, and IKK-γ (NEMO)[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
16713556
reach
"In the absence of any robust stimulation of NF-kappaB (such as TCR engagement or cytokine signaling), CYLD deubiquitylates TRAF2, TRAF6, and NEMO, dampening NF-kappaB signaling by removing activating K63 chains formed by TRAF2/6."
26732666
reach
"Under normal conditions, the ubiquitination of TRAF2 is suppressed by CYLD."
40102846
reach
"CYLD attenuates NF-κB activity by regulating the ubiquitination of NEMO, TRAF2, TRAF6, and TAK1, which are important signaling elements constituting the NF-κB pathway [ 16–18 ]."
35131382
reach
"Notably, CYLD physically interacts with and deubiquitinates TRAF2, an E3 ubiquitin–protein ligase that modifies itself with Lys63-linked ubiquitin chains."
15571815
reach
"CYLD knockout increases ubiquitination of TRAF2, leading to sustained JNK signaling, which subsequently upregulates cyclin D1 and c-Myc expression [46]."
35884607
reach
"For example, CYLD inhibits the ubiquitination of TRAF2 and NEMO to negatively regulate the activation of NF-κB by TLR and TNF signaling [58–60] ."
23415874
Modified CYLD leads to the deubiquitination of TRAF2. 2 / 2
| 2
reach
"Indeed, immunoprecipitation analysis showed that overexpression of CYLD induced deubiquitination of TRAF2 in ECs."
18245814
reach
"Of importance, overexpression of catalytically inactive CYLD did not induce deubiquitination of TRAF2."
18245814
Mutated CYLD leads to the deubiquitination of TRAF2. 1 / 1
| 1
reach
"When these serines are mutated to alanines, it generates a super-active CYLD mutant that prevents TNF-alpha-stimulated TRAF2 ubiquitination."
19373246
CYLD ubiquitinates TRAF2.
| 12 1
CYLD ubiquitinates TRAF2. 10 / 12
| 10 1
reach
"CYLD can inhibit NF-kappaB activity by deubiquitinating and inactivating TRAF2 and TRAF6, RIP, NEMO, and the NF-kappaB co-activator BCL-3."
18718859
reach
"We show that CYLD binds to the NEMO (also known as IKKgamma) component of the IkappaB kinase (IKK) complex, and appears to regulate its activity through de-ubiquitination of TRAF2, as TRAF2 ubiquitination can be modulated by CYLD."
12917690
sparser
"Ubiquitination of TRAF2 by CYLD was found to be nearly abolished in the presence of a dominant negative ubiquitin-specific protease mutant deficient in CYLD ( xref )."
27508514
reach
"In immune signaling, CYLD negatively regulates NF-κB by deubiquitinating TRAF2, TRAF6, TAK1, and NEMO (29–32)."
39958342
reach
"CYLD knockdown by siRNA results in constitutive ubiquitination of TRAF2."
19373246
reach
"CYLD mediated regulation of the JNK signaling pathway appears to target TRAF2 ubiquitylation, as CYLD knockdown increases both TRAF2 ubiquitylation and JNK activation, further enhancing cell survival [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
20347313
reach
"A20 also suppresses necroptosis by deubiquitinating RIPK3 at K5, whereas CYLD mediates necroptotic effects by deubiquitinating TNF receptor associated factor 2 (TRAF2)."
27959630
reach
"Ubiquitination of TRAF2 by CYLD was found to be nearly abolished in the presence of a dominant negative ubiquitin specific protease mutant deficient in CYLD."
27508514
reach
"CYLD binds to the NEMO (also known as IKKg) component of the IkB kinase (IKK) complex and appears to regulate its activity through de-ubiquitination of TRAF2, since the ubiquitination of TRAF2 can be [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
16153642
reach
"A series of recent reports have shown that CYLD blocks signal transmission through the classical NF-κB cascade by deubiquitinating the TNF receptor-associated factor 2 (TRAF2), TRAF6, and IKK-γ (NEMO)[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
16713556
CYLD sumoylated on K40 leads to the ubiquitination of TRAF2. 1 / 1
| 1
reach
"Similarly, SUMOylation of CYLD at K40 can reduce the efficiency of CYLD-mediated deubiquitination of TRAF2 and TRAF6 (Kobayashi et al., 2015)."
37387450
CYLD-S418A leads to the ubiquitination of TRAF2. 1 / 1
| 1
reach
"In constrast, cotransfection of CYLD S418A with IKKepsilon did not block deubiquitination of TRAF2 (XREF_FIG)."
19481526
CYLD inhibits TRAF2.
1 | 7 3
CYLD inhibits TRAF2. 10 / 14
1 | 7 3
reach
"Thus, CYLD inhibits MyD88, RIP1 (receptor-interacting serine/threonine-protein kinase 1), TRAF2, TRAF6, TRAF7, and NEMO downstream to TLR signaling and regulates exaggerated inflammation which can lea[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
33075714
sparser
"CYLD also inhibits TRAF2 and NEMO (NF-κB essential modulator, a regulatory subunit of IKK), and blocks NF-κB signaling downstream to TLR activation [176-178] ."
33075714
reach
"Phosphorylation at S418 weakens the catalytic efficiency of CYLD, which impairs the degradation of its substrates TRAF2 and TRAF6 and, consequently, promotes NF-κB signalling."
37387450
sparser
"Similarly to active-site C601 CYLD mutants ( Trompouki et al. , 2003 ; this work), CYLD-D681G was unable to inhibit TRAF2- or TRAF6-mediated activation of NF- κ B and TNF α activation of JNK, and to[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17851586
reach
"CYLD was shown to inactivate TRAF2, TRAF6, and IKKγ by removing the K63-linked polyubiquitin chains ( Kovalenko et al., 2003 ), whereas A20 removes K63-linked polyubiquitin chains from TRAF2, TRAF6, a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17098202
reach
"Similarly, de-ubiquitinating enzyme cylindromatosis (CYLD) inhibits NF-kappaB signaling via de-ubiquitination and inactivation of TNFR associated factor 2 (TRAF2) and TRAF6 [XREF_BIBR, XREF_BIBR]; de-ubiquitinating protease A20 inhibits NF-kappaB activation induced by Toll like receptor 4 (TLR4) via removing K63 linked polyubiquitin chains of TRAF6 [XREF_BIBR]."
27164085
reach
"Similarly, another DUB, cylindromatosis (CYLD), functions as a tumor suppressor and eliminates K63-linked Ub molecules from TNFR-associated factor 2 (TRAF2) [182]."
34814083
sparser
"CYLD also inhibits TRAF2 and NEMO (NF-κB essential modulator, a regulatory subunit of IKK), and blocks NF-κB signaling downstream to TLR activation [176] [177] [178] ."
| DOI
reach
"CYLD also inhibits TRAF2 and NEMO (NF-kappaB essential modulator, a regulatory subunit of IKK), and blocks NF-kappaB signaling downstream to TLR activation [176] [177] [178]."
| DOI
reach
"CYLD also inhibits TRAF2 and NEMO (NF-κB essential modulator, a regulatory subunit of IKK), and blocks NF-κB signaling downstream to TLR activation [176-178] ."
33075714
CYLD activates TRAF2.
| 3
CYLD activates TRAF2. 3 / 3
| 3
reach
"Also, CYLD knocking-out macrophages could increase JNK activity through ubiquitinizing TRAF-2 protein, and studies have confirmed that CYLD knocking-out mice were prone to cancers [11, 12]."
38246916
reach
"The regulation of TRAF2 signaling by CYLD was identified by screening an RNAi library targeting DUBs for ones that attenuate NFkappaB activation [XREF_BIBR] and through a two-hybrid screen for proteins that interact with the regulatory subunit of the IkappaB kinase complex that could also bind to TRAF2 [XREF_BIBR]."
19007437
reach
"In contrast to earlier studies, which had shown that CYLD acts as a Lys-63-specific DUB, Xue et al. found that CYLD removes Lys 48 polyubiquitin chains from TRAF2, thereby preventing TRAF2 proteolytic[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
20347313
TRAF2 affects CYLD
7 1 | 16 27
TRAF2 binds CYLD.
7 1 | 16 26
TRAF2 binds CYLD. 10 / 42
7 1 | 14 18
reach
"A point mutation in CYLD that abolishes CYLD binding to TRAF2 greatly increases polyubiquitin-TRAF2 levels."
15571815
sparser
"Surprisingly, however, CYLDex7/8 mutant HSCs did not significantly activate the NF-κB pathway, but instead p38MAPK signaling, indicating that CYLD–TRAF2 interactions elicit a signaling cascade that is HSC specific."
25824820
sparser
"Lacking of exons 7 and 8 of Cyld (Cyld ex7/8 ) abrogates the interaction of CYLD-NEMO and CYLD-TRAF2 ( xref )."
38562929
reach
"Notably, CYLD physically interacts with and deubiquitinates TRAF2, an E3 ubiquitin–protein ligase that modifies itself with Lys63-linked ubiquitin chains."
15571815
sparser
"CYLD interacts directly with TRAF2, an adaptor molecule involved in signaling by members of the family of TNF/nerve growth factor receptors ( xref , xref )."
19489724
reach
"Mechanistically, CYLD binds to NEMO and TRAF2 and reverses non-K48-linked polyubiquitination of TRAF2, thereby blocking TRAF2 mediated activation of the IKK complex [XREF_BIBR - XREF_BIBR] (XREF_FIG)."
27844253
sparser
"CYLD also binds the TNF receptor–associated factor 2, which is an upstream activator of IKK."
15100680
sparser
"Our study adds a novel level of complexity to this scenario, revealing that the interaction between the DUB CYLD and the adaptor protein, E3 ubiquitin ligase TRAF2, elicits a signaling pathway that promotes dormancy and thus prevents HSCs from unscheduled proliferation and exhaustion."
25824820
sparser
"Although our CYLDex7/8 mouse model indicates that the TRAF2-binding domain is crucial to control HSC function by promoting the interaction between CYLD and TRAF2, we cannot formally exclude that unknown substrates bind to this domain as well."
25824820
reach
"Interestingly, CYLD interacts with NEMO and TRAF2, both of which are recruited to the TNF receptor upon ligand binding."
14676304
CYLD binds IKBKG and TRAF2. 3 / 3
| 3
sparser
"The direct interaction of CYLD with both TRAF2 and NEMO is facilitated by N-terminal protein-protein interaction domains and contributes to its activity toward these substrates ( Kovalenko et al., 200[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18313383
sparser
"Mechanistically, CYLD binds to NEMO and TRAF2 and reverses non-K48-linked polyubiquitination of TRAF2, thereby blocking TRAF2-mediated activation of the IKK complex [ xref - xref ] ( xref )."
27844253
sparser
"Interestingly, CYLD interacts with NEMO (IKKγ; references xref – xref ) and TRAF2 ( xref , xref ), both of which are recruited to the TNF receptor upon ligand binding."
14676304
RIPK1 binds TRAF2 and CYLD. 2 / 2
| 2
sparser
"TNFα treatment increases the binding between PrP and the deubiquitinase tumor suppressor cylindromatosis (CYLD), in these treated cells, binding of CYLD to RIP1 and TRAF2 is reduced."
28900035
sparser
"Interactions between CYLD and RIP1 or TRAF2 were specific as isotype controls did not pull down any CYLD ( xref , A and B )."
28900035
CYLD binds TRAF2 and K63. 1 / 1
| 1
reach
"When CYLD associates with TRAF2, it removes the K63 and M1 poly-ubiquitin chains from RIPK1, thereby allowing RIPK1 to dissociate from the TNFR1 complex."
33324405
TRAF2 binds IKBKG, BCL3, and CYLD. 1 / 1
| 1
sparser
"In addition to these well-defined protein domains, new domains of CYLD have been defined, based on mutational analyses, for the interaction of CYLD with TRAF2, IKKγ and BCL-3 (Refs xref , xref )."
18535581
TNFAIP3 binds CYLD, TNFRSF9, and TRAF2. 1 / 1
| 1
sparser
"The deubiquitinases A20 and CYLD interact with the 4-1BB and TRAF2 complex and, by regulating the ubiquitination of TRAF2 and TAK1 ( xref ), they decrease 4-1BB activation [ xref ]."
| PMC
IKK_complex binds TRAF2, TRAF6, and CYLD. 1 / 1
| 1
sparser
"The initial clue to the signaling function of CYLD came from an RNAi-based functional screening study, which identified CYLD as a DUB that negatively regulates NF- κ B activation. xref At the same time, yeast two-hybrid screening studies identified CYLD as a protein that binds to NF- κ B essential modulator (NEMO), a regulatory subunit of I κ B kinase (IKK). xref , xref CoIP assays also revealed the association of CYLD with two IKK regulatory proteins, TRAF2 and TRAF6, and subsequent studies identified additional molecular targets of CYLD ( xref )."
19373246
TRAF2 binds mutated CYLD. 1 / 1
| 1
reach
"The biochemical analysis using phosphomimetic mutants demonstrated that this PTM negatively affects the deubiquitinating activity of CYLD on TRAF2, most likely through interfering with the catalytic activity of CYLD, since the binding of TRAF2 to a CYLD mutant mimicking phosphorylation on Ser 418 is not affected."
21480003
TRAF2 ubiquitinates CYLD.
| 1
TRAF2 ubiquitinates CYLD. 1 / 1
| 1
sparser
"CYLD-mediated regulation of the JNK signaling pathway appears to target TRAF2 ubiquitylation, as CYLD knockdown increases both TRAF2 ubiquitylation and JNK activation, further enhancing cell survival [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
20347313
sparser
"The 21 core genes associated with the RIG-I-like receptor signaling pathway included IFIH1, TRIM25, NFKB1, DHX58, DDX3X, IRF7, ISG15, DDX58, TRAF2, MAPK11, RELA, CXCL8, TBK1, IL12B, RIPK1, NFKBIA, CYLD, IL12A, TNF, AZI2 , and TANK ."
34490145