Heterologous SUMO-2/3-ubiquitin chains optimize IκBα degradation and NF-κB activity.
Heterologous SUMO-2/3-ubiquitin chains optimize IκBα degradation and NF-κB activity.
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DOI：
10.1371/journal.pone.0051672
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Lang V
中科院分区：
文献类型：
--
作者：
Aillet F;Lopitz-Otsoa F;Egaña I;Hjerpe R;Fraser P;Hay RT;Rodriguez MS;Lang V
NF-κB途径至少在三个水平上受SUMO化调控：抑制分子IκBα、IKK亚单位γ/NEMO和p52前体P100。在此，我们研究了SUMO-2/3在IκBα降解和肿瘤坏死因子κα介导的核转录因子B活化中的作用。我们发现，在SUMO化不足的条件下，肿瘤坏死因子α介导的IκBα的蛋白分解和依赖于NF-κB的转录都发生了重要的延迟。体外和体外方法，包括使用泛素陷阱(管)的使用，揭示了IκBα在肿瘤坏死因子α刺激后形成含有SUMO-2/3和泛素的链。整合SUMO-2/3似乎促进了IκBα激活肿瘤坏死因子α信号通路后泛素链的形成。此外，与单独的SUMO-2/3或泛素相比，SUMO-2/3和泛素的异源链在体外可以更有效地促进26S蛋白酶体对IκBα的降解。Ubc9沉默一贯地减少了用蛋白酶体介导的缺陷蛋白酶体降解的相扑-泛素杂合链修饰的IκBα的捕获。因此，杂交的SUMO-2/3-泛素链增加了修饰的IκBα对26S蛋白酶体作用的敏感性，有助于在肿瘤坏死因子κ刺激后对NF-αB的活性进行最佳控制。
The NF-κB pathway is regulated by SUMOylation at least at three levels: the inhibitory molecule IκBα, the IKK subunit γ/NEMO and the p52 precursor p100. Here we investigate the role of SUMO-2/3 in the degradation of IκBα and activation of NF-κB mediated by TNFα. We found that under conditions of deficient SUMOylation, an important delay in both TNFα-mediated proteolysis of IκBα and NF-κB dependent transcription occurs. In vitro and ex vivo approaches, including the use of ubiquitin-traps (TUBEs), revealed the formation of chains on IκBα containing SUMO-2/3 and ubiquitin after TNFα stimulation. The integration of SUMO-2/3 appears to promote the formation of ubiquitin chains on IκBα after activation of the TNFα signalling pathway. Furthermore, heterologous chains of SUMO-2/3 and ubiquitin promote a more efficient degradation of IκBα by the 26S proteasome in vitro compared to chains of either SUMO-2/3 or ubiquitin alone. Consistently, Ubc9 silencing reduced the capture of IκBα modified with SUMO-ubiquitin hybrid chains that display a defective proteasome-mediated degradation. Thus, hybrid SUMO-2/3-ubiquitin chains increase the susceptibility of modified IκBα to the action of 26S proteasome, contributing to the optimal control of NF-κB activity after TNFα-stimulation.
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影响因子：
3.7
作者：
Da Silva-Ferrada E;Torres-Ramos M;Aillet F;Campagna M;Matute C;Rivas C;Rodríguez MS;Lang V
通讯作者：
Lang V
影响因子：
4.1
作者：
Dorval, Veronique;Mazzella, Matthew J.;Fraser, Paul E.
通讯作者：
Fraser, Paul E.
影响因子：
3.6
作者：
Kim, Eun Mi;Lee, Han-Hyoung;Chun, Taehoon
通讯作者：
Chun, Taehoon
影响因子：
4.8
作者：
Coux, O;Goldberg, AL
通讯作者：
Goldberg, AL
影响因子：
64.8
作者：
Ikeda, Fumiyo;Deribe, Yonathan Lissanu;Skanland, Sigrid S.;Stieglitz, Benjamin;Grabbe, Caroline;Franz-Wachtel, Mirita;van Wijk, Sjoerd J. L.;Goswami, Panchali;Nagy, Vanja;Terzic, Janos;Tokunaga, Fuminori;Androulidaki, Ariadne;Nakagawa, Tomoko;Pasparakis, Manolis;Iwai, Kazuhiro;Sundberg, John P.;Schaefer, Liliana;Rittinger, Katrin;Macek, Boris;Dikic, Ivan
通讯作者：
Dikic, Ivan