TNF and IL-1 exhibit distinct ubiquitin requirements for inducing NEMO-IKK supramolecular structures.
TNF and IL-1 exhibit distinct ubiquitin requirements for inducing NEMO-IKK supramolecular structures.
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DOI：
10.1083/jcb.201307172
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发表时间：
2014-01-20
期刊：
影响因子：
--
通讯作者：
Laplantine E
中科院分区：
文献类型：
--
作者：
Tarantino N;Tinevez JY;Crowell EF;Boisson B;Henriques R;Mhlanga M;Agou F;Israël A;Laplantine E
NEMO募集到超分子复合物的机制及其对泛素化的依赖在对促炎细胞因子TNF和IL-1的反应中有所不同。核因子κB （NF-κB）必需调节剂（NEMO）是i -κB激酶（IKK）复合物的调节组分，通过与泛素链的相互作用控制NF-κB的活化。我们在这里表明，白细胞介素-1 （IL-1）和TNF的刺激诱导NEMO快速和短暂地募集到锚定在细胞周围的点状结构中。这些结构富含活化的IKK激酶和泛素化的NEMO分子，这表明它们是NF-κB活化的组织中心。这些含有nemo的结构与活化的TNF受体共定位，但不与活化的IL-1受体共定位。我们利用缺乏K63泛素链或线性泛素链组装复合物（LUBAC）介导的线性泛素化的细胞，研究了非降解泛素化在这些结构形成中的作用。我们的研究结果表明，与TNF不同，IL-1需要k63连接的线性泛素链将NEMO招募到高阶复合物中。因此，NEMO被募集到超分子复合物中涉及不同的机制，这似乎是NF-κB活化所必需的。
The mechanism of NEMO recruitment into supramolecular complexes and its dependence on ubiquitination differs in response to the proinflammatory cytokines TNF and IL-1. Nuclear factor κB (NF-κB) essential modulator (NEMO), a regulatory component of the IκB kinase (IKK) complex, controls NF-κB activation through its interaction with ubiquitin chains. We show here that stimulation with interleukin-1 (IL-1) and TNF induces a rapid and transient recruitment of NEMO into punctate structures that are anchored at the cell periphery. These structures are enriched in activated IKK kinases and ubiquitinated NEMO molecules, which suggests that they serve as organizing centers for the activation of NF-κB. These NEMO-containing structures colocalize with activated TNF receptors but not with activated IL-1 receptors. We investigated the involvement of nondegradative ubiquitination in the formation of these structures, using cells deficient in K63 ubiquitin chains or linear ubiquitin chain assembly complex (LUBAC)-mediated linear ubiquitination. Our results indicate that, unlike TNF, IL-1 requires K63-linked and linear ubiquitin chains to recruit NEMO into higher-order complexes. Thus, different mechanisms are involved in the recruitment of NEMO into supramolecular complexes, which appear to be essential for NF-κB activation.
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影响因子：
3.4
作者：
Qian, H;SHEETZ, MP;ELSON, EL
通讯作者：
ELSON, EL
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影响因子：
16
作者：
Lo, Yu-Chih;Lin, Su-Chang;Rospigliosi, Carla C.;Conze, Dietrich B.;Wu, Chuan-Jin;Ashwell, Jonathan D.;Eliezer, David;Wu, Hao
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作者：
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影响因子：
5.3
作者：
Conze, Dietrich B.;Wu, Chuan-Jin;Ashwell, Jonathan D.
通讯作者：
Ashwell, Jonathan D.