IndraLab

Statements

TRAF2 binds CYLD. 32 / 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
reach
"We found that in the absence of PrP, binding between CYLD and TRAF2 was slightly enhanced by TNFalpha treatment (XREF_FIG A)."
28900035
reach
"Interactions between CYLD and RIP1 or TRAF2 were specific as isotype controls did not pull down any CYLD (XREF_FIG, A and B)."
28900035
reach
"In contrast, under TNFalpha treatment, binding between CYLD and RIP1 or TRAF2 was reduced, if the cells also expressed PrP (XREF_FIG B)."
28900035
reach
"Although after 100 d of chase (+ doxycycline) 11.0 +/- 2.3% of CYLDex7/8 WT SKLCD150 + CD48 - CD34 - cells retained the H2B-GFP label, only 5.6 +/- 1.02% of mutant cells remained GFP positive (XREF_FIG), demonstrating that CYLD binding to TRAF2 is a crucial step to maintain HSC dormancy."
25824820
sparser
"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 (Fig. xref a; [ xref ])."
21480003
reach
"Thus, in the presence of PrP, TNFalpha treatment increased the interaction between PrP and CYLD but alleviated binding between CYLD and RIP1 or TRAF2."
28900035
reach
"It was also shown that CYLD, a de-ubiquitinase known to remove K63 linked polyubiquitin chains from other proteins, binds TRAF2 [68]."
26993379
reach
"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 can not formally exclude that unknown substrates bind to this domain as well."
25824820
sparser
"This phenotype is dependent on the interactions between CYLD and its substrate TRAF2 (tumor necrosis factor–associated factor 2)."
25824820
sparser
"Unexpectedly, the robust cycling of HSCs lacking functional CYLD–TRAF2 interactions was not elicited by increased NF-κB signaling, but instead by increased activation of the p38MAPK pathway."
25824820
sparser
"Mechanistically, our data show that the CYLD–TRAF2 interaction is crucial to maintain dHSCs as it precludes p38MAPK activation, down-regulation of dormancy-associated genes, and entry of dHSCs into the cell cycle, ultimately preventing HSC exhaustion."
25824820
sparser
"To investigate whether the interactions between CYLD and TRAF2 are important to preserve the pool of dHSCs, we crossed CYLDex7/8 mutant animals with SCL-tTA;H2B-GFP mice and again performed label-retaining assays ( xref )."
25824820
sparser
"Although after 100 d of chase (+doxycycline) 11.0 ± 2.3% of CYLDex7/8 WT SKLCD150 + CD48 − CD34 − cells retained the H2B-GFP label, only 5.6 ± 1.02% of mutant cells remained GFP positive ( xref ), demonstrating that CYLD binding to TRAF2 is a crucial step to maintain HSC dormancy."
25824820
sparser
"Thus, the loss of HSC dormancy that occurs in these mice is most likely solely caused by an impaired CYLD–TRAF2 interaction."
25824820
sparser
"We thus investigated whether the impaired CYLD–TRAF2 interactions may alter p38MAPK activity."
25824820
sparser
"Under resting conditions, CYLD interacts with TRAF2. xref Following stimulation, LUBAC is recruited to the TNF-R-signaling complex (TNF-Rsc) through TRADD, TRAF2, and c-IAP interaction and c-IAP-generated ubiquitin chains xref ( xref )."
35958947
sparser
"A point mutation in CYLD that abolishes CYLD binding to TRAF2 greatly increases polyubiquitin-TRAF2 levels."
15571815
sparser
"It is well established that CYLD interacts with TRAF2, causing deubiquitination of both TRAF2 and RIP1 44,47–50 and that activation of CYLD can block NF-κB activation induced by TNF-α stimulation."
16936264
sparser
"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 ( xref , xref )."
33324405
reach
"TNFalpha 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
reach
"CYLD interacts directly with TRAF2, an adaptor molecule involved in signaling by members of the family of TNF and nerve growth factor receptors."
19489724
reach
"To investigate whether the interactions between CYLD and TRAF2 are important to preserve the pool of dHSCs, we crossed CYLDex7/8 mutant animals with SCL-tTA; H2B-GFP mice and again performed label retaining assays."
25824820