Regulatory Effects of Ribosomal S6 Kinase 1 (RSK1) in IFNλ Signaling
Regulatory Effects of Ribosomal S6 Kinase 1 (RSK1) in IFNλ Signaling
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DOI：
10.1074/jbc.m110.183566
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发表时间：
2011-01-14
影响因子：
4.8
通讯作者：
Platanias, Leonidas C.
中科院分区：
文献类型：
--
作者：
Kroczynska, Barbara;Joshi, Sonali;Platanias, Leonidas C.
虽然已经鉴定了控制III型IFN（IFN λ）调节基因转录激活的信号产生机制，但是关于IFN λ受体产生IFN λ激活基因mRNA翻译信号的机制知之甚少。我们提供的证据表明，干扰素λ激活p90核糖体蛋白S6激酶1（RSK 1）及其下游效应，起始因子eIF 4 B。在与IFN λ受体结合之前，RSK 1的非活性形式与IFN λ敏感细胞中的翻译阻遏物4 E-BP 1形成复合物。RSK 1的IFN α诱导的磷酸化/活化导致其与4 E-BP 1解离，同时4 E-BP 1与eIF 4 E解离，以允许形成eIF 4F并启动帽依赖性翻译。我们的研究表明，这样的干扰素依赖性的RSK 1的参与是必不可少的上调p21（WAF 1/CIP 1）的表达，这表明产生生长抑制反应的机制。总而言之，我们的数据提供了证据，激活RSK 1在IFN λ信号转导中的关键作用。
Although the mechanisms of generation of signals that control transcriptional activation of Type III IFN (IFN lambda)-regulated genes have been identified, very little is known about the mechanisms by which the IFN lambda receptor generates signals for mRNA translation of IFN lambda-activated genes. We provide evidence that IFN lambda activates the p90 ribosomal protein S6 kinase 1 (RSK1) and its downstream effector, initiation factor eIF4B. Prior to its engagement by the IFN lambda receptor, the non-active form of RSK1 is present in a complex with the translational repressor 4E-BP1 in IFN lambda-sensitive cells. IFN lambda-inducible phosphorylation/activation of RSK1 results in its dissociation from 4E-BP1 at the same time that 4E-BP1 dissociates from eIF4E to allow formation of eIF4F and initiation of cap-dependent translation. Our studies demonstrate that such IFN lambda-dependent engagement of RSK1 is essential for up-regulation of p21(WAF1/CIP1) expression, suggesting a mechanism for generation of growth-inhibitory responses. Altogether, our data provide evidence for a critical role for the activated RSK1 in IFN lambda signaling.