A central role of IKK2 and TPL2 in JNK activation and viral B-cell transformation.,Nature Communications

当前位置： X-MOL 学术 › Nat. Commun. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

A central role of IKK2 and TPL2 in JNK activation and viral B-cell transformation.
Nature Communications ( IF 14.7 ) Pub Date : 2020-02-04 , DOI: 10.1038/s41467-020-14502-x
Stefanie Voigt ₁ , Kai R Sterz ₁ , Fabian Giehler _{1,

2} , Anne-Wiebe Mohr _{1,

2} , Joanna B Wilson ₃ , Andreas Moosmann _{1,

2,

4} , Arnd Kieser _{1,

2}

Affiliation

IκB kinase 2 (IKK2) is well known for its pivotal role as a mediator of the canonical NF-κB pathway, which has important functions in inflammation and immunity, but also in cancer. Here we identify a novel and critical function of IKK2 and its co-factor NEMO in the activation of oncogenic c-Jun N-terminal kinase (JNK) signaling, induced by the latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV). Independent of its kinase activity, the TGFβ-activated kinase 1 (TAK1) mediates LMP1 signaling complex formation, NEMO ubiquitination and subsequent IKK2 activation. The tumor progression locus 2 (TPL2) kinase is induced by LMP1 via IKK2 and transmits JNK activation signals downstream of IKK2. The IKK2-TPL2-JNK axis is specific for LMP1 and differs from TNFα, Interleukin-1 and CD40 signaling. This pathway mediates essential LMP1 survival signals in EBV-transformed human B cells and post-transplant lymphoma, and thus qualifies as a target for treatment of EBV-induced cancer.

中文翻译：

IKK2和TPL2在JNK激活和病毒B细胞转化中的核心作用。

IκB激酶2（IKK2）以其作为经典NF-κB通路的介质发挥关键作用而闻名，该通路在炎症和免疫以及癌症中具有重要作用。在这里，我们确定了IKK2及其辅助因子NEMO在致癌性c-Jun N末端激酶（JNK）信号激活中的新型和关键功能，该信号由爱泼斯坦-巴尔病毒（EBV）的潜在膜蛋白1（LMP1）诱导）。TGFβ激活的激酶1（TAK1）与其激酶活性无关，介导LMP1信号复合物的形成，NEMO泛素化和随后的IKK2激活。LMP1通过IKK2诱导肿瘤进展基因2（TPL2）激酶，并在IKK2下游传递JNK激活信号。IKK2-TPL2-JNK轴是LMP1特有的，不同于TNFα，白介素-1和CD40信号传导。

更新日期：2020-02-04

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南