Mechanisms of proinflammatory cytokine-induced biphasic NF-κB activation
Mechanisms of proinflammatory cytokine-induced biphasic NF-κB activation
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DOI：
10.1016/s1097-2765(03)00390-3
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发表时间：
2003-11-01
期刊：
影响因子：
16
通讯作者：
Chiao, PJ
中科院分区：
文献类型：
--
作者：
Schmidt, C;Peng, BL;Chiao, PJ
转录因子NF-kappaB调控与先天和获得性免疫反应、炎症、细胞凋亡和肿瘤发生有关的基因。促炎细胞因子在短暂期和持续期诱导核因子-kappaB的激活。我们研究了这种双相核因子-kappaB激活的机制。我们的结果表明，MEKK3在调节核因子-kappaB的快速激活中是必不可少的，而MEKK2在控制核因子-kappaB在细胞因子TNF-α和IL-1α刺激下的延迟激活中起重要作用。MEKK3参与IkappaBalpha：NF-kappaB/IKK复合体的形成，而MEKK2参与组装IkappaBbeta：NF-kappaB/IKK复合体；这两个不同的复合体调节促炎细胞因子诱导的双相NF-kappaB激活。因此，我们的研究揭示了一种新的机制，即不同的MAP3K和IkappaB亚型参与与IKK和NF-kappaB形成特定的复合体，以调节双相NF-kappaB的激活。这些发现为细胞因子诱导的特定和时间基因表达的调控提供了进一步的洞察力。
The transcription factor NF-kappaB regulates genes involved in innate and adaptive immune response, inflammation, apoptosis, and oncogenesis. Proinflammatory cytokines induce the activation of NF-kappaB in both transient and persistent phases. We investigated the mechanism for this biphasic NF-kappaB activation. Our results show that MEKK3 is essential in the regulation of rapid activation of NF-kappaB, whereas MEKK2 is important in controlling the delayed activation of NF-kappaB in response to stimulation with the cytokines TNF-alpha and IL-1alpha. MEKK3 is involved in the formation of the IkappaBalpha:NF-kappaB/IKK complex, whereas MEKK2 participates in assembling the IkappaBbeta:NF-kappaB/IKK complex; these two distinct complexes regulate the proinflammatory cytokine-induced biphasic NF-kappaB activation. Thus, our study reveals a novel mechanism in which different MAP3K and IkappaB isoforms are involved in specific complex formation with IKK and NF-kappaB for regulating the biphasic NF-kappaB activation. These findings provide further insight into the regulation of cytokine-induced specific and temporal gene expression.