2017
DOI: 10.1101/gad.299776.117
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SPATA2 regulates the activation of RIPK1 by modulating linear ubiquitination

Abstract: Stimulation of cells with TNFα leads to the formation of the TNF-R1 signaling complex (TNF-RSC) to mediate downstream cellular fate decision. Activation of the TNF-RSC is modulated by different types of ubiquitination and may lead to cell death, including apoptosis and necroptosis, in both RIPK1-dependent and RIPK1-independent manners. Spata2 (spermatogenesis-associated 2) is an adaptor protein recruited into the TNF-RSC to modulate the interaction between the linear ubiquitin chain assembly complex (LUBAC) an… Show more

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Cited by 54 publications
(60 citation statements)
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“…However, SPATA2 silencing did not significantly alter the abundance of MIB1 and PCM1, suggesting SPATA2-independent functions for CYLD in this context ( Figures S4F and S4G). Further supporting this idea, Spata2 knockout mice do not display the characteristic ciliopathies-related symptoms seen in Cyld knockout animals (Wei et al, 2017). Altogether, our data suggest that CYLD removes K 63 -linked ubiquitin chains bound to MIB1.…”
Section: Cyld Directly Deubiquitinates the Centriolar Satellites Gatesupporting
confidence: 78%
“…However, SPATA2 silencing did not significantly alter the abundance of MIB1 and PCM1, suggesting SPATA2-independent functions for CYLD in this context ( Figures S4F and S4G). Further supporting this idea, Spata2 knockout mice do not display the characteristic ciliopathies-related symptoms seen in Cyld knockout animals (Wei et al, 2017). Altogether, our data suggest that CYLD removes K 63 -linked ubiquitin chains bound to MIB1.…”
Section: Cyld Directly Deubiquitinates the Centriolar Satellites Gatesupporting
confidence: 78%
“…Data information: For all Immunoblotting data, molecular weights in kDa are indicated to the left. Source data are available online for this figure. function of Spata2 is to act as a CYLD partner protein that recruits CYLD to TNFSC complex for deubiquitination of RIP1 and initiation of necroptosis Kupka et al, 2016;Wagner et al, 2016;Wei et al, 2017). The results presented in this paper established Spata2 as a novel regulator of NLRP3 inflammasome activation and inflammatory responses.…”
Section: Discussionmentioning
confidence: 57%
“…Spata2 has been implicated in the regulation of TNFα‐induced cell death and NF‐κB activation, although the latter function has been controversial (Elliott et al , ; Kupka et al , ; Schlicher et al , ; Wagner et al , ; Wei et al , ). To investigate the in vivo function of Spata2, we generated Spata2 knockout (KO) mice.…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…S3C). In addition, no difference in the recruitment of Sharpin, a key component of the M1ubiquitinating LUBAC complex, which suppresses RIPK1 activation (25), was found in complex I of WT Ripk1 and Ripk1 K584R/K584R MEFs (Fig. S3D).…”
Section: Ripk1 K584r Knockin Mutation Blocks Necroptosis and Ripk1-dementioning
confidence: 97%