IndraLab

Statements


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reach
"Here, we identify SPATA2 as a constitutive direct binding partner of HOIP that bridges the interaction between CYLD and HOIP."

sparser
"However, the binding systems differ in that OTULIN directly binds to HOIP via the PIM motif of OTULIN [ xref , xref , xref ], whereas CYLD interacts with HOIP through spermatogenesis-associated 2 (SPATA2) [ xref , xref , xref , xref ]."
| PMC

reach
"Unexpectedly, CYLD was recently reported to interact with HOIP, the catalytic subunit of LUBAC, and to inhibit LUBAC dependent activation of NF-kappaB."

reach
"Interestingly, CYLD also binds the HOIP PUB and B-box domains despite lacking a discernible PIM."

reach
"Together, these results show that CYLD and OTULIN interact with HOIP via the same or an overlapping site and that HOIP 's interactions with CYLD and OTULIN are mutually exclusive."

sparser
"In this study, we report that HOIP also interacts with the deubiquitinase CYLD but that CYLD does not regulate ubiquitination of LUBAC components."

sparser
"SPATA2 mediates the recruitment of CYLD to immune receptor complexes by bridging the interaction of CYLD with the linear ubiquitylation assembly complex (LUBAC) component HOIP."

No evidence text available

reach
"We here show that CYLD interacts with HOIP via spermatogenesis associated protein 2 (SPATA2)."

No evidence text available

reach
"OTULIN and CYLD bind HOIP in a mutually exclusive manner (71)."

reach
"The linear ubiquitin chain assembly complex (LUBAC) regulates immune signaling, and its function is regulated by the deubiquitinases OTULIN and CYLD, which associate with the catalytic subunit HOIP."

sparser
"The search for such a factor resulted in the discovery of SPATA2 as a previously unrecognized component of the TNFR1-SC and NOD2-SC, which bridges the interaction between CYLD and HOIP by directly interacting, via distinct domains, with both proteins."

sparser
"Kupka et al. show that the previously demonstrated interaction of CYLD with HOIP, which is required for recruitment of CYLD into signaling complexes, is indirect and mediated by SPATA2."

reach
"Furthermore, in cells expressing HOIP-N102A, which can interact with neither CYLD nor OTULIN, CYLD is not recruited to the TNF-RSC, demonstrating that CYLD 's interaction with HOIP is essential for CYLD recruitment."

reach
"Additionally, when we overexpressed CYLD in HOIP-TAP-expressing cells, we found that overexpression only marginally increased the amount of CYLD bound to HOIP as compared to endogenous levels of CYLD (XREF_FIG C)."

reach
"An interaction between HOIP and OTULIN or CYLD seems strange, since their highly specific yet counteracting activities would generate a futile energy consuming circle."

sparser
"In cells, CYLD interaction with HOIP depends on the PIM-binding pocket within the HOIP PUB domain ( xref , xref , xref )."

reach
"HOIP interacts with both CYLD and OTULIN even in unstimulated cells."

sparser
"Intriguingly, although the interaction of OTULIN with HOIP has been shown to be direct and was structurally characterized ( xref , xref ), we were not able to detect direct binding of CYLD to HOIP."

reach
"In this study, we report that HOIP also interacts with the deubiquitinase CYLD but that CYLD does not regulate ubiquitination of LUBAC components."

reach
"Intriguingly, although the interaction of OTULIN with HOIP has been shown to be direct and was structurally characterized, we were not able todetect direct binding of CYLD to HOIP."

reach
"Mutually Exclusive Binding of CYLD and OTULIN to HOIP Causes CYLD Selective Recruitment to SCs."

reach
"However, the mechanism through which CYLD interacts with HOIP is unclear."

reach
"In line with recent reports, our data showed that prior to stimulation, both CYLD and OTULIN interacted with HOIP (XREF_SUPPLEMENTARY B-S1D)."

sparser
"This prompted us to search for a protein that would mediate the interaction between CYLD and HOIP."

sparser
"However, the mechanism through which CYLD interacts with HOIP is unclear."

reach
"SPATA2 Mediated Binding of CYLD to HOIP Enables CYLD Recruitment to Signaling Complexes."

sparser
"Mammalian HOIP does not bind CYLD directly, and instead, the two proteins are linked by SPATA2, which contains a predicted PUB domain in its N‐terminus that interacts with CYLD, while its C‐terminal portion is recognized by the N‐terminus of HOIP xref ."

No evidence text available

sparser
"Here, we show that CYLD does not interact directly with HOIP and identify the uncharacterized protein spermatogenesis-associated protein 2 (SPATA2) as the factor that bridges CYLD and HOIP."

sparser
"Together, these results show that SPATA2 contains two distinct domains that are responsible for mediating the interaction with CYLD and HOIP, respectively; while the N terminus of SPATA2 binds to the USP domain of CYLD, the interaction with HOIP is mediated via a highly conserved PIM located in the central portion of SPATA2, which is recognized by the PUB domain of HOIP."

No evidence text available

reach
"Recruitment of CYLD, HOIP and Sharpin to TNF-RSC in response to TNFalpha was not affected in RIPK1 S321A (A/A) MEFs."

No evidence text available

sparser
"Additionally, when we overexpressed CYLD in HOIP-TAP-expressing cells, we found that overexpression only marginally increased the amount of CYLD bound to HOIP as compared to endogenous levels of CYLD ( xref C)."

No evidence text available

sparser
"Strikingly, the association of CYLD with HOIP drastically increased when SPATA2 was also overexpressed ( xref C)."

sparser
"This suggested that the interaction between HOIP and CYLD is mediated by an additional factor, and we were therefore prompted to test whether SPATA2 may function as an adaptor."

reach
"This prompted us to search for a protein that would mediate the interaction between CYLD and HOIP."

sparser
"Here, we identify SPATA2 as a constitutive direct binding partner of HOIP that bridges the interaction between CYLD and HOIP."

sparser
"If this were the case, the interaction of HOIP and CYLD should increase as a function of co-overexpression of SPATA2."

reach
"In cells, CYLD interaction with HOIP depends on the PIM binding pocket within the HOIP PUB domain."

No evidence text available

sparser
"Accordingly, when we reduced SPATA2 levels by RNAi and immunoprecipitated overexpressed FLAG-tagged HOIP, the amount of CYLD associated with HOIP was drastically decreased ( xref D)."

reach
"The search for such a factor resulted in the discovery of SPATA2 as a previously unrecognized component of the TNFR1-SC and NOD2-SC, which bridges the interaction between CYLD and HOIP by directly interacting, via distinct domains, with both proteins."

sparser
"Given that, LUBAC may form a putative complex which includes both OTULIN and CYLD bound to two HOIP molecules [ xref , xref ]."

sparser
"This requires the adaptor protein SPATA2, bridging the interaction between CYLD and HOIP ( xref ; xref ; xref ; xref ; xref )."

sparser
"The linear ubiquitin chain assembly complex (LUBAC) regulates immune signaling, and its function is regulated by the deubiquitinases OTULIN and CYLD, which associate with the catalytic subunit HOIP."

reach
"If this were the case, the interaction of HOIP and CYLD should increase as a function of co-overexpressionofSPATA2."

No evidence text available

reach
"In contrast to these findings, Draber et al. demonstrated that, although both OTULIN and CYLD interact with HOIP under basal conditions, OTULIN is absent from RSCs [XREF_BIBR] and that knock-out of OTULIN resulted in an increase of Met1 linked poly-Ub chains in the cytosol but not at TNFR1 or NOD2 RSCs [XREF_BIBR]."