Activation of the c-Jun NH(2)-terminal kinase pathway by coronavirus infectious bronchitis virus promotes apoptosis independently of c-Jun.

Activation of the c-Jun NH(2)-terminal kinase pathway by coronavirus infectious bronchitis virus promotes apoptosis independently of c-Jun.
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DOI:
10.1038/s41419-017-0053-0
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发表时间:
2017-12-13
影响因子:
9
通讯作者:
Liu DX
Liu DX
中科院分区:
生物学1区
文献类型:
--
作者:
Fung TS;Liu DX

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丝裂原活化蛋白激酶(MAPKs)是一种保守的蛋白激酶,可调节多种重要的细胞信号通路。其中,已知c-Jun n -末端激酶(JNK)可被包括病毒感染在内的各种环境胁迫激活。此前,在几种冠状病毒感染的细胞中检测到JNK通路的激活。然而,该途径的详细特征及其在宿主-病毒相互作用中的意义尚未得到充分研究。在这里,我们报道了JNK通路在感染了禽冠状病毒传染性支气管炎病毒(IBV)的细胞中被激活。在已知的两种上游MAPK激酶(MKK)中,MKK7,而不是MKK4,被证明是ibv诱导的JNK激活的原因。此外,敲低和过表达实验表明,JNK在IBV感染过程中发挥促凋亡蛋白的作用。有趣的是,JNK的促凋亡活性不是通过c-Jun介导的,而是参与了抗凋亡蛋白b细胞淋巴瘤2 (Bcl2)的调节。综上所述,JNK与其他mapk一起构成了冠状病毒与宿主相互作用的一个重要方面。
Mitogen-activated protein kinases (MAPKs) are conserved protein kinases that regulate a variety of important cellular signaling pathways. Among them, c-Jun N-terminal kinases (JNK) are known to be activated by various environmental stresses including virus infections. Previously, activation of the JNK pathway has been detected in cells infected with several coronaviruses. However, detailed characterization of the pathway as well as its implication in host–virus interactions has not been fully investigated. Here we report that the JNK pathway was activated in cells infected with the avian coronavirus infectious bronchitis virus (IBV). Of the two known upstream MAPK kinases (MKK), MKK7, but not MKK4, was shown to be responsible for IBV-induced JNK activation. Moreover, knockdown and overexpression experiments demonstrated that JNK served as a pro-apoptotic protein during IBV infection. Interestingly, pro-apoptotic activity of JNK was not mediated via c-Jun, but involved modulation of the anti-apoptotic protein B-cell lymphoma 2 (Bcl2). Taken together, JNK constitutes an important aspect of coronavirus–host interaction, along with other MAPKs.
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