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TRAF Family Member-associated NF-kappa B Activator (TANK) Inhibits Genotoxic Nuclear Factor kappa B Activation by Facilitating Deubiquitinase USP10-dependent Deubiquitination of TRAF6 Ligase 期刊论文

编号：

6d8803c9-1d55-410b-89ba-05e35d92ea21
作者：

Wang, Wei^[1,2] Huang, Xuan^[3] Xin, HongBo^[3] Fu, Mingui^[4] Xue, Aimin^[5] Wu, ZhaoHui^[1,2]
语种：

English
期刊：

JOURNAL OF BIOLOGICAL CHEMISTRY ISSN：0021-9258 2015 年 290 卷 21 期 (13372 - 13385) ; MAY 22
收录：
摘要：

DNA damage-induced NF-kappa B 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-kappa B signaling cascade are poorly understood. We recently demonstrated that genotoxic NF-kappa B activation is regulated by reversible ubiquitination of several essential mediators involved in this signaling pathway. Here we show that TRAF family member-associated NF-kappa B activator (TANK) negatively regulates NF-kappa B 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-kappa B activation upon DNA damage. Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated deletion of TANK in human cells significantly enhanced NF-kappa B 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-1 beta or LPS. In accordance, depletion of USP10 enhanced NF-kappa B activation induced by IL-1 beta or LPS. Collectively, our data demonstrate that TANK serves as an important negative regulator of NF-kappa B signaling cascades induced by genotoxic stress and IL-1R/Toll-like receptor stimulation in a manner dependent on MCPIP1/USP10-mediated TRAF6 deubiquitination.
推荐引用方式
GB/T 7714：

Wang Wei,Huang Xuan,Xin Hong-Bo, et al. TRAF Family Member-associated NF-kappa B Activator (TANK) Inhibits Genotoxic Nuclear Factor kappa B Activation by Facilitating Deubiquitinase USP10-dependent Deubiquitination of TRAF6 Ligase [J].JOURNAL OF BIOLOGICAL CHEMISTRY,2015,290(21):13372-13385.
APA：

Wang Wei,Huang Xuan,Xin Hong-Bo,Fu Mingui,&Wu Zhao-Hui.(2015).TRAF Family Member-associated NF-kappa B Activator (TANK) Inhibits Genotoxic Nuclear Factor kappa B Activation by Facilitating Deubiquitinase USP10-dependent Deubiquitination of TRAF6 Ligase .JOURNAL OF BIOLOGICAL CHEMISTRY,290(21):13372-13385.
MLA：

Wang Wei, et al. "TRAF Family Member-associated NF-kappa B Activator (TANK) Inhibits Genotoxic Nuclear Factor kappa B Activation by Facilitating Deubiquitinase USP10-dependent Deubiquitination of TRAF6 Ligase" .JOURNAL OF BIOLOGICAL CHEMISTRY 290,21(2015):13372-13385.

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