IndraLab

Statements

ITCH binds CYLD. 32 / 32
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"Here, we demonstrate that Itch interacts with Cyld and cooperatively regulates Tak1 and inflammation."
22057290
reach
"At present the molecular mechanisms that regulate Itch and Cyld complex formation remain unclear."
22057290
sparser
"Itch interacts with Cyld via the WW-PPXY motifs."
22057290
sparser
"Here, we demonstrate that Itch interacts with Cyld and cooperatively regulates Tak1 and inflammation."
22057290
reach
"Taken together these data collectively indicate that Itch forms a complex with Cyld via its interaction through ' PPXY ' motif."
22057290
sparser
"To further confirm the role of Itch and Cyld interaction for terminating Tak1 activation in macrophages, we reconstituted Cyld −/− BMDMs with Cyld(WT) or Cyld(Y485A) mutant that fails to interact with Itch."
22057290
sparser
"Taken together these data collectively indicate that Itch forms a complex with Cyld via its interaction through ‘PPXY’ motif."
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"Ahmed et al. demonstrated that Itch forms a complex with the deubiquitinase Cyld downstream of TNFalpha signaling in bone marrow derived macrophages (BMDMs), and that this complex, much like the A20 complex, replaces a K63 linked ubiquitin chain with a degradative K48 linked chain."
32356405
sparser
"To test whether Itch-Cyld interaction occurs via the ‘PPXY’ motif, we generated Y to A mutant Cyld (Cyld(Y485A)) by site-directed mutagenesis."
22057290
biogrid
No evidence text available
22057290
sparser
"Itch and Cyld interaction in BMDMs seems to be stimulation dependent as we did not detect the association in unstimulated cells (data not shown)."
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"GST-Itch precipitated His Cyld in the pull-down assay confirming a direct interaction between Itch and Cyld (XREF_FIG)."
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"Here we demonstrate that E3 ligase Itch and deubiquitinase Cyld formed a complex via interaction through ' WW-PPXY ' motifs."
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sparser
"Antibody against Myc immunoprecipitated Flag-Itch and vice versa , suggesting that Itch physically interacts with Cyld ( xref )."
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sparser
"DUB-E3 interactions are used for mutual ubiquitin-dependent regulation (e.g., to control each other’s stability, see above) or for editing ubiquitin chain architecture on particular substrates (as shown for the hybrid DUB/E3 enzyme A20 and CYLD-ITCH complexes during inflammatory signaling [ xref , xref ])."
33335288
sparser
"MDM2 can increase NF-κB activity [ xref ], and the ITCH-CYLD protein complex terminates NF-κB activation via Tak1 [ xref ]."
| PMC
biogrid
No evidence text available
22057290
sparser
"The Cyld(Y485A) mutation disrupted Itch-Cyld interaction ( xref )."
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"Itch and Cyld complex edits Tak1 ubiquitination."
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sparser
"The mechanistic study showed that ITCH is complexed with CYLD to promote the transition of K63-linkage to K48-linkage via sequentially cleaving the K63-linked ubiquitin chain followed by catalyzing K48- linked ubiquitination on the TAK1 protein."
32165318
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"E3 ligase Itch and deubiquitinase CYLD form a complex that cleaves lysine (Lys) 63 linked ubiquitin chains and catalyze Lys48 linked ubiquitination on the kinase Tak1, which is a common substrate for these two proteins, thereby contributing to decreased inflammatory signalling [XREF_BIBR]."
23151130
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"Next, we sought to understand the role of Itch and Cyld complex in the regulation of inflammatory response."
22057290
biogrid
No evidence text available
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"In addition, an Itch and CYLD complex promotes the transition of K63 linked ubiquitinylation to K48 linked ubiquitinylation by sequentially cleaving the K63 linked ubiquitin chain and catalysing K48 l[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24418622
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"This finding suggests that Itch and Cyld complex degrades the Tak1 that is associated with TRAF complex but not the entire pool of Tak1 within the cell during an inflammatory response."
22057290
sparser
"Ahmed et al. demonstrated that Itch forms a complex with the deubiquitinase Cyld downstream of TNF α signaling in bone marrow-derived macrophages (BMDMs), and that this complex, much like the A20 complex, replaces a K63-linked ubiquitin chain with a degradative K48-linked chain."
32356405
sparser
"Reconstitution of wild-type Cyld but not mutant Cyld(Y485A), which cannot associate with Itch, blocked the sustained Tak1 activation and proinflammatory cytokine production by Cyld −/− bone marrow-derived macrophages."
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"Itch interacts with Cyld via the WW-PPXY motifs."
22057290
sparser
"To determine whether Itch and Cyld can directly interact with each other, we performed sequence analysis and found a highly conserved Cyld ‘PPXY’ motif ( xref ) by which it could interact with Itch ‘WW’ domains."
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"Recently, it has been demonstrated that E3 ligase ITCH and CYLD formed a complex which can sequentially cleave K63 linked ubiquitin-chain and catalyzes K48 linked ubiquitination to deactivate TAK1 and terminate NF-kappaB signaling, providing an example of how K48 and K63 linked ubiquitinations are closely linked and can be differentially utilized to control kinase activation and deactivation."
22649774
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"Itch and Cyld complex promotes the transition of K63 linked to K48 linked ubiquitination by sequentially cleaving K63 linked ubiquitin chain and by catalyzing K48 linked ubiquitination on Tak1."
22057290
sparser
"GST-Itch precipitated His-Cyld in the pull-down assay confirming a direct interaction between Itch and Cyld ( xref )."
22057290