IndraLab

Statements

SPATA2 binds CYLD. 47 / 56
8 | 1 8 30
sparser
"The binding of SPATA2‐CYLD or OTULIN to HOIP was shown to be mutually exclusive (Draber et al , xref ; Schlicher et al , xref )."
35170849
sparser
"The mechanisms regulating the interaction of LUBAC with OTULIN and SPATA2-CYLD in cells are not well-understood but in vitro studies show that phosphorylation of the tyrosine (Y56) in the OTULIN PIM abrogates its interaction with HOIP, suggesting that this may be a mechanism to regulate the LUBAC–OTULIN complex [32]."
33473179
sparser
"LUBAC co-recruits SPATA2-CYLD to receptor signalling complexes where CYLD regulates Lys63-and Met1-Ub of substrates and thereby inflammatory and cell death signalling decisions [31, 33, 35, 57]."
33473179
sparser
"These results were corroborated by in vitro pull-downs and surface plasmon resonance (SPR), which revealed the CYLD-SPATA2 interaction to be high affinity (96 nM), and also showed no binding of the isolated B-box domain to SPATA2 ( xref C, 3D, xref D, and S3E)."
27591049
biogrid
No evidence text available
19615732
sparser
"Our data indicate that CYLD-SPATA2, the IKK complex members, and WHIP itself are significantly enriched in isolates of endogenous UBASH3B. Using synthetic peptides spiked into the sample to perform absolute quantification of endogenously expressed proteins, we found that the binding of TNF-RSC components to UBASH3B was, with the exception of ubiquitin, highly substoichiometric ( xref )."
36179048
sparser
"The mechanisms regulating the interaction of LUBAC with OTULIN and SPATA2-CYLD in cells are not well-understood but in vitro studies show that phosphorylation of the tyrosine (Y56) in the OTULIN PIM abrogates its interaction with HOIP, suggesting that this may be a mechanism to regulate the LUBAC–OTULIN complex [ xref ]."
33473179
biogrid
No evidence text available
27458237
sparser
"In line with the in vitro analysis, substitution of the conserved Tyr338 in the SPATA2 PIM to Ala (Y338A) or Phe (Y338F) largely abrogated the interaction of SPATA2 with HOIP in cells, without affecting SPATA2 binding to CYLD ( xref G)."
27591049
sparser
"The PUB domain of HOIP can also interact with SPATA2 that binds CYLD and thereby bridges this deubiquitinase to LUBAC (Elliott et al., xref ; Kupka et al., xref ; Schlicher et al., xref ; Wagner et al., xref )."
31998699
sparser
"Importantly, LUBAC binds negative regulators of deubiquitinases (DUBs), such as OTULIN and the CYLD-SPATA2 complex, through the N-terminal PUB domain of HOIP ( xref – xref )."
33329596
sparser
"The Met1-Ub machinery (LUBAC, OTULIN, and CYLD-SPATA2) generates (and removes) Met1-Ub."
33473179
reach
"In line with the invitro analysis, substitution of the conserved Tyr338 in the SPATA2 PIM to Ala (Y338A) or Phe (Y338F) largely abrogated the interaction of SPATA2 with HOIP in cells, without affecting SPATA2 binding to CYLD (XREF_FIG G)."
27591049
sparser
"It is possible that SPATA2 binding to a CYLD dimer creates additional interactions that stabilize the hetero-tetrameric complex, and further structural work is required to illuminate this."
27591049
sparser
"Hence, CYLD and SPATA2 form a highly stable heterotetramer in vitro and likely in cells, which is destabilized when the core dimerization domain, the B-box of CYLD, is deleted or disrupted."
27591049
reach
"SPATA2 Binds CYLD in a B-box-Dependent Manner."
27591049
biogrid
No evidence text available
27591049
sparser
"In the absence of OTULIN, only CYLD-SPATA2-LUBAC complexes can form [ xref – xref ], and conversely, without CYLD, only OTULIN-LUBAC complexes can assemble [ xref – xref ]."
32231246
sparser
"Characterization of the CYLD-SPATA2 Interaction."
27591049
sparser
"To do this, we focused on CYLD-SPATA2, which is substoichiometric with respect to the TNFR1 receptor."
36179048
sparser
"OTULIN-released LUBAC interacts with SPATA2 and is recruited to the TNF-R1sc, facilitating SPATA2-CYLD interaction."
35958947
sparser
"Strikingly, SPATA2 did not interact with monomeric CYLD ΔB-box, and while the CYLD-SPATA2 binding interface does not appear to involve the B-box itself, SPR measurements reveal diminished complex stability when CYLD is monomeric."
27591049
sparser
"This could be due to LUBAC in cells interacting with cellular components such as SPATA2 and CYLD ( xref ; xref ; xref ; xref )."
34142657
reach
"Although LUBEL apparently lacks the PUB domain found in HOIP (Fig XREF_FIG A), which is important for recruiting a SPATA2 and CYLD complex in mammals 36, we could detect an interaction between the LUBEL-RBR-C domain and dCYLD in pulldown experiments (Fig XREF_FIG C and D)."
27702987
biogrid
No evidence text available
19615732
sparser
"The binding of MALT1 to the HOIP PUB domain did not disturb the association with OTULIN ( xref ), indicating that MALT1 simultaneously binds LUBAC with DUBs, such as OTULIN and CYLD-SPATA2, through the HOIP PUB domain."
33329596
sparser
"The interaction between SPATA2 and CYLD was confirmed in cells by co-immunoprecipitation of ectopic or endogenous proteins ( xref F and 1G)."
27591049
reach
"Moreover, co-expression of V5 tagged HOIP and SPATA2 variants showed that the SPATA2 PIM is needed to co-immunoprecipitate CYLD and HOIP, demonstrating that the CYLD and SPATA2 complex is linked to LUBAC via the SPATA2 PIM-HOIP PUB interaction (XREF_FIG H)."
27591049
sparser
"In keeping with this, our iBAQ analysis indicates that only ∼20 to 25% of LUBAC molecules are bound to CYLD-SPATA2 ()."
36179048
biogrid
No evidence text available
27591049
sparser
"LUBAC exists in distinct complexes with the DUBs OTULIN (1) and CYLD-SPATA2 (2)."
33473179
reach
"In accordance with the mass spectrometry experiments and the affinity of the CYLD and SPATA2 interaction, this suggests that a substantial fraction of the cellular pool of CYLD is in complex with SPATA2, which links it to LUBAC and possibly other high-order complexes."
27591049
trips
"SPATA2 links CYLD to the TNF-α receptor signaling complex and modulates the receptor signaling outcomes."
27307491
biogrid
No evidence text available
27591049
reach
"The SPATA2 and CYLD complex also plays a role in the TNF dependent apoptosis pathway [XREF_BIBR]."
28446710
sparser
"Since we know that 1) CYLD and SPATA2 are bound in a 2:2 stoichiometry ( xref and) ( xref ), 2) endogenous CYLD and LUBAC components are more abundant than SPATA2 in the proteome profiling of 29 human tissues (), and 3) SPATA2 mediates CYLD recruitment to LUBAC ( xref , xref ), we would predict that only part of the cytoplasmic pool of CYLD is bound to SPATA2 and that as a consequence, CYLD-SPATA2 complex is substoichiometrically bound to the LUBAC complex."
36179048
sparser
"DUBs, such as OTULIN and the CYLD-SPATA2 complex, bind to the PUB domain of HOIP and downregulate NF-κB activity by hydrolyzing the ubiquitin chains ( xref – xref )."
33329596
reach
"The N-terminal portion of HOIP contains a PNGase and UBA or UBX (PUB) domain (XREF_FIG), which is reportedly an AAA-ATPase p97 interacting domain [XREF_BIBR] that plays an important role to recruit linear ubiquitin editing DUBs, such as OTULIN [XREF_BIBR] and the CYLD and SPATA2 complex [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR]."
32403254
biogrid
No evidence text available
27458237
biogrid
No evidence text available
27591049
sparser
"SPATA2 interacts with CYLD through its non-canonical PUB domain, which binds the catalytic CYLD USP domain in a CYLD B-box-dependent manner."
27591049
reach
"The interaction between SPATA2 and CYLD was confirmed in cells by co-immunoprecipitation of ectopic or endogenous proteins (XREF_FIG F and 1G)."
27591049
sparser
"The N-terminal portion of HOIP contains a PNGase/UBA or UBX (PUB) domain ( xref ), which is reportedly an AAA-ATPase p97-interacting domain [ xref ] that plays an important role to recruit linear ubiquitin-editing DUBs, such as OTULIN [ xref ] and the CYLD-SPATA2 complex [ xref , xref , xref , xref ]."
32403254
sparser
"LUBAC co-recruits SPATA2-CYLD to receptor signalling complexes where CYLD regulates Lys63-and Met1-Ub of substrates and thereby inflammatory and cell death signalling decisions [ xref , xref , xref , xref ]."
33473179
sparser
"Our data consistently identify CYLD-SPATA2 as limiting members ( xref and, red dot), and, on average, indicate that most complexes are present in less than one or at most one copy per receptor, even at the peak of recruitment (10 min)."
36179048
sparser
"Fig. 2: LUBAC exists in distinct complexes with the DUBs OTULIN (1) and CYLD-SPATA2 (2)."
33473179
sparser
"The B-box dependence of the CYLD-SPATA2 interaction ( xref B, 1C, and 1F) could suggest a direct interaction between the B-box and the SPATA2 PUB domain."
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