Grass carp (Ctenopharyngodon idella) STAT3 regulates the eIF2a
Grass carp (Ctenopharyngodon idella) STAT3 regulates the eIF2a
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草鱼 (Ctenopharyngodon idella) STAT3 调节 eIF2a
DOI：
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发表时间：
2017
影响因子：
2.9
通讯作者：
liqiang wang
中科院分区：
文献类型：
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作者：
liqiang wang
在哺乳动物中，STAT 3（Signal transducer and activator of transcription 3）在生长、增殖、分化中起重要作用，并参与炎症、肿瘤发生、代谢紊乱和免疫应答。STAT 3是一种在细胞核和细胞质之间穿梭的蛋白质。与细胞核中的STAT 3相比，细胞质中的STAT 3的功能长期以来并不清楚。最近的一些研究表明，细胞质STAT 3通过与双链RNA激活蛋白激酶（PKR）的相互作用来调节自噬，PKR在细胞抗病毒反应中发挥重要作用。鱼类是发育免疫学和比较免疫学的良好靶点。在本研究中，我们发现草鱼（Ctenopharyngodon idella）STAT 3（CiSTAT 3）的表达是普遍存在的，并且在poly I：C的刺激下显著上调。为了探讨鱼类细胞质中STAT 3在抗病毒信号通路中的潜在功能，本文分析了鱼类细胞质中的CiSTAT 3与CiPKR之间的关系。我们证明了CiSTAT 3可以在体内和体外与CiPKR联合收割机结合。CiSTAT 3的SH 2结构域和CiPKR的C-末端在该过程中起重要作用。在正常情况下，CiSTAT 3和CiPKR形成二聚体，而在poly I：C的诱导下，CiSTAT 3和CiPKR的二聚体解离。因此，我们推测CiSTAT 3和CiPKR的结合可能调节细胞活力。还显示CIK细胞中CiSTAT 3的过表达可显著降低p-eIF 2a的水平。相反，CIK细胞中siRNA介导的CiSTAT 3敲低和Stattic诱导可上调p-eIF 2a水平。为了进一步理解CiSTAT 3和p-eIF 2a水平之间的关系，我们进行了CiPKR敲低实验。结果表明，CiSTAT 3通过与CiPKR结合来调节p-eIF 2a的水平。此外，在CIK细胞中过表达CiSTAT 3能够提高细胞活力。以上结果揭示了鱼类细胞质STAT 3调控eIF 2a磷酸化和细胞活力的分子机制。因此，鱼类细胞质STAT 3的功能与哺乳动物相似。
In mammals, STAT3 (Signal transducer and activator of transcription 3) plays an important role in.growth, multiplication, differentiation and participates in inflammation, tumorigenesis, metabolic disorders and immune response. STAT3 is a protein that shuttles between the nucleus and cytoplasm..Compared to the STAT3 in cell nucleus, we did not know the function of STAT3 in cytoplasm for a long.time. Some recent studies have shown that cytoplasmic STAT3 regulates autophagy through the interaction with the double-stranded RNA-activated protein kinase (PKR), which plays an important role in.cellular antiviral response. Fish is a good target for developmental and comparative immunology. In the.present study, we found that the expression of grass carp (Ctenopharyngodon idella) STAT3 (CiSTAT3) was.ubiquitous and significantly up-regulated under the stimulation of poly I:C. To explore the potential.function of fish cytoplasmic STAT3 in the antiviral signaling pathways, in this paper we analyzed the.relationship between cytoplasmic CiSTAT3 and CiPKR. We demonstrated that the CiSTAT3 can combine.with CiPKR in vivo and in vitro. The SH2 domain of CiSTAT3 and the C-terminus of CiPKR play an.important role in this process. Moreover, the dimer of CiSTAT3 and CiPKR was formed under normal.circumstances, however, it was dissociated under the induction of poly I:C. So, we guessed the binding of.CiSTAT3 and CiPKR may regulate cell viability. It has also been shown that overexpression of CiSTAT3 in.CIK cells can significantly reduce the level of p-eIF2a. On the contrary, the siRNA-mediated knockdown of.CiSTAT3 and Stattic induction in CIK cells can up-regulate the p-eIF2a level. To further understand the.relationship between CiSTAT3 and p-eIF2a level, we carried out the CiPKR-knockdown experiment. The.result indicated that CiSTAT3 regulated the level of p-eIF2a through binding to CiPKR. In addition,.overexpression of CiSTAT3 in CIK cells was able to improve the cell viability. These results above.unraveled the molecular mechanism of fish cytoplasmic STAT3 regulating the eIF2a phosphorylation and.cell viability. Therefore, the function of fish cytoplasmic STAT3 is similar to those of mammals.