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http://purl.uniprot.org/citations/25861989http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25861989http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25861989http://www.w3.org/2000/01/rdf-schema#comment"DNA damage-induced NF-κB activation plays a critical role in regulating cellular response to genotoxic stress. However, the molecular mechanisms controlling the magnitude and duration of this genotoxic NF-κB signaling cascade are poorly understood. We recently demonstrated that genotoxic NF-κB activation is regulated by reversible ubiquitination of several essential mediators involved in this signaling pathway. Here we show that TRAF family member-associated NF-κB activator (TANK) negatively regulates NF-κB activation by DNA damage via inhibiting ubiquitination of TRAF6. Despite the lack of a deubiquitination enzyme domain, TANK has been shown to negatively regulate the ubiquitination of TRAF proteins. We found TANK formed a complex with MCPIP1 (also known as ZC3H12A) and a deubiquitinase, USP10, which was essential for the USP10-dependent deubiquitination of TRAF6 and the resolution of genotoxic NF-κB activation upon DNA damage. Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated deletion of TANK in human cells significantly enhanced NF-κB activation by genotoxic treatment, resulting in enhanced cell survival and increased inflammatory cytokine production. Furthermore, we found that the TANK-MCPIP1-USP10 complex also decreased TRAF6 ubiquitination in cells treated with IL-1β or LPS. In accordance, depletion of USP10 enhanced NF-κB activation induced by IL-1β or LPS. Collectively, our data demonstrate that TANK serves as an important negative regulator of NF-κB signaling cascades induced by genotoxic stress and IL-1R/Toll-like receptor stimulation in a manner dependent on MCPIP1/USP10-mediated TRAF6 deubiquitination."xsd:string
http://purl.uniprot.org/citations/25861989http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m115.643767"xsd:string
http://purl.uniprot.org/citations/25861989http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m115.643767"xsd:string
http://purl.uniprot.org/citations/25861989http://purl.uniprot.org/core/author"Huang X."xsd:string
http://purl.uniprot.org/citations/25861989http://purl.uniprot.org/core/author"Huang X."xsd:string
http://purl.uniprot.org/citations/25861989http://purl.uniprot.org/core/author"Fu M."xsd:string
http://purl.uniprot.org/citations/25861989http://purl.uniprot.org/core/author"Fu M."xsd:string
http://purl.uniprot.org/citations/25861989http://purl.uniprot.org/core/author"Wang W."xsd:string
http://purl.uniprot.org/citations/25861989http://purl.uniprot.org/core/author"Wang W."xsd:string
http://purl.uniprot.org/citations/25861989http://purl.uniprot.org/core/author"Wu Z.H."xsd:string
http://purl.uniprot.org/citations/25861989http://purl.uniprot.org/core/author"Wu Z.H."xsd:string
http://purl.uniprot.org/citations/25861989http://purl.uniprot.org/core/author"Xin H.B."xsd:string
http://purl.uniprot.org/citations/25861989http://purl.uniprot.org/core/author"Xin H.B."xsd:string
http://purl.uniprot.org/citations/25861989http://purl.uniprot.org/core/author"Xue A."xsd:string
http://purl.uniprot.org/citations/25861989http://purl.uniprot.org/core/author"Xue A."xsd:string
http://purl.uniprot.org/citations/25861989http://purl.uniprot.org/core/date"2015"xsd:gYear
http://purl.uniprot.org/citations/25861989http://purl.uniprot.org/core/date"2015"xsd:gYear
http://purl.uniprot.org/citations/25861989http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/25861989http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/25861989http://purl.uniprot.org/core/pages"13372-13385"xsd:string
http://purl.uniprot.org/citations/25861989http://purl.uniprot.org/core/pages"13372-13385"xsd:string
http://purl.uniprot.org/citations/25861989http://purl.uniprot.org/core/title"TRAF family member-associated NF-kappaB activator (TANK) inhibits genotoxic nuclear factor kappaB activation by facilitating deubiquitinase USP10-dependent deubiquitination of TRAF6 ligase."xsd:string
http://purl.uniprot.org/citations/25861989http://purl.uniprot.org/core/title"TRAF family member-associated NF-kappaB activator (TANK) inhibits genotoxic nuclear factor kappaB activation by facilitating deubiquitinase USP10-dependent deubiquitination of TRAF6 ligase."xsd:string
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