Crosstalk Between NDP52 and LUBAC in Innate Immune Responses, Cell Death, and Xenophagy.
Crosstalk Between NDP52 and LUBAC in Innate Immune Responses, Cell Death, and Xenophagy.
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NDP52和Lubac之间的串扰，在先天免疫反应，细胞死亡和Xenophapy中。
DOI：
10.3389/fimmu.2021.635475
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发表时间：
2021
影响因子：
7.3
通讯作者：
Tokunaga F
中科院分区：
文献类型：
--
作者：
Miyashita H;Oikawa D;Terawaki S;Kabata D;Shintani A;Tokunaga F
核点蛋白52 kDa（NDP 52，也称为CALCOCO 2）作为选择性自噬受体发挥作用。线性泛素链组装复合物（LUBAC）特异性地产生N-末端Met 1连接的线性泛素链，并调节天然免疫应答，如核因子-κB（NF-κB）、干扰素（IFN）抗病毒和凋亡途径。虽然NDP 52和LUBAC合作调节细菌入侵诱导的异食，但它们的功能串扰仍然是个谜。在这里，我们发现NDP 52通过C-末端UBZ结构域的广泛特异性泛素结合抑制典型的NF-κB信号传导。在TNF-α刺激后，NDP 52通过HOIP亚基与LUBAC结合，但不干扰其泛素连接酶活性，并通过作为TNF-α受体信号传导复合物I的组分对NF-κB活化具有适度抑制作用。NDP 52还调节TNF-α诱导的凋亡途径，但不调节阿霉素诱导的内源性凋亡。LUBAC的化学抑制剂（HOIPIN-8）取消了NF-κB和IFN抗病毒途径的增加的活化，并增强了NDP 52敲除和NDP 52敲减的HeLa细胞的凋亡。沙门氏菌感染后，共定位沙门氏菌，LC 3，和线性泛素检测到在亲本HeLa细胞诱导异嗜。用HOIPIN-8处理扰乱了共定位并促进了沙门氏菌的扩增。相比之下，HOIPIN-8对NDP 52敲除细胞中LC 3和沙门氏菌的共定位几乎没有影响，这表明NDP 52在LUBAC介导的异嗜中是弱调节剂。这些结果表明，NDP 52和LUBAC之间的串扰调节先天免疫应答、细胞凋亡和异嗜性。
Nuclear dot protein 52 kDa (NDP52, also known as CALCOCO2) functions as a selective autophagy receptor. The linear ubiquitin chain assembly complex (LUBAC) specifically generates the N-terminal Met1-linked linear ubiquitin chain, and regulates innate immune responses, such as nuclear factor-κB (NF-κB), interferon (IFN) antiviral, and apoptotic pathways. Although NDP52 and LUBAC cooperatively regulate bacterial invasion-induced xenophagy, their functional crosstalk remains enigmatic. Here we show that NDP52 suppresses canonical NF-κB signaling through the broad specificity of ubiquitin-binding at the C-terminal UBZ domain. Upon TNF-α-stimulation, NDP52 associates with LUBAC through the HOIP subunit, but does not disturb its ubiquitin ligase activity, and has a modest suppressive effect on NF-κB activation by functioning as a component of TNF-α receptor signaling complex I. NDP52 also regulates the TNF-α-induced apoptotic pathway, but not doxorubicin-induced intrinsic apoptosis. A chemical inhibitor of LUBAC (HOIPIN-8) cancelled the increased activation of the NF-κB and IFN antiviral pathways, and enhanced apoptosis in NDP52-knockout and -knockdown HeLa cells. Upon Salmonella-infection, colocalization of Salmonella, LC3, and linear ubiquitin was detected in parental HeLa cells to induce xenophagy. Treatment with HOIPIN-8 disturbed the colocalization and facilitated Salmonella expansion. In contrast, HOIPIN-8 showed little effect on the colocalization of LC3 and Salmonella in NDP52-knockout cells, suggesting that NDP52 is a weak regulator in LUBAC-mediated xenophagy. These results indicate that the crosstalk between NDP52 and LUBAC regulates innate immune responses, apoptosis, and xenophagy.
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DOI：
10.1007/s00018-016-2191-4
发表时间：
2016-06
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Dondelinger Y;Darding M;Bertrand MJ;Walczak H
通讯作者：
Walczak H
影响因子：
8
作者：
Inomata, Megumi;Niida, Shumpei;Shibata, Ken-ichiro;Into, Takeshi
通讯作者：
Into, Takeshi
影响因子：
13.3
作者：
Cemma, Marija;Kim, Peter Kijun;Brumell, John Hunter
通讯作者：
Brumell, John Hunter
影响因子：
64.8
作者：
Huttlin EL;Bruckner RJ;Paulo JA;Cannon JR;Ting L;Baltier K;Colby G;Gebreab F;Gygi MP;Parzen H;Szpyt J;Tam S;Zarraga G;Pontano-Vaites L;Swarup S;White AE;Schweppe DK;Rad R;Erickson BK;Obar RA;Guruharsha KG;Li K;Artavanis-Tsakonas S;Gygi SP;Harper JW
通讯作者：
Harper JW
NDP52 的分子特征，NDP52 是核结构域 10 的一种新型蛋白质，在病毒感染和干扰素治疗后重新分布。
DOI：
10.1083/jcb.130.1.1
发表时间：
1995-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Korioth F;Gieffers C;Maul GG;Frey J
通讯作者：
Frey J