Phosphorylation of the HuR ligand APRIL by casein kinase 2 regulates CD83 expression
Phosphorylation of the HuR ligand APRIL by casein kinase 2 regulates CD83 expression
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DOI：
10.1002/eji.200838619
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发表时间：
2009-01-01
影响因子：
5.4
通讯作者：
Hauber, Joachim
中科院分区：
文献类型：
--
作者：
Chemnitz, Jan;Pieper, Dorothea;Hauber, Joachim
完全成熟的 DC 以及在较小程度上活化的 T 和 B 细胞表达 CD83，CD83 是一种表面分子，似乎在有效的 T 细胞激活中发挥着重要作用。最近，研究表明 CD83 mRNA 通过一种不常见的途径从细胞核转运到细胞质，涉及细胞 RNA 结合蛋白 HuR 和核输出受体 CRM1。此外，穿梭磷蛋白 APRIL (ANP32B) 已被证明是 HuR 介导的 CD83 mRNA 核质易位所必需的，可作为连接 HuR 和 CRM1 的接头。在这里，我们能够报告酪蛋白激酶 2 (CK2) 在残基苏氨酸 244 (Thr(244)) 上磷酸化 APRIL，并证明 CK2 特异性抑制剂 4,5,6,7-tetrabromo-2-azabenzimidazole 通过干扰 CD83 mRNA 的核质转位来消除活化的 Jurkat T 细胞中的 CD83 表达。耗竭和敲除研究表明，CK2α'亚基对于这种调节是必需的，而CK2α亚基似乎是可有可无的。总而言之，所提供的数据显着扩展了我们对 CD83 mRNA 加工复杂调节的认识，并提供了干扰 CD83 表达的新策略。
Fully mature DC and, to a lesser extent, activated T and B cells express CD83, a surface molecule that appears to fulfil an important role in efficient T-cell activation. Recently, it has been shown that CD83 mRNA is transported from the nucleus to the cytoplasm by an uncommon route, involving the cellular RNA-binding protein HuR and the nuclear export receptor CRM1. Moreover, the shuttle phosphoprotein APRIL (ANP32B) has been shown to be required for HuR-mediated nucleocytoplasmic translocation of the CD83 mRNA by acting as an adaptor that links HuR and CRM1. Here, we are able to report that casein kinase 2 (CK2) phosphorylates APRIL on residue threonine244 (Thr(244)) and demonstrate that the CK2-specific inhibitor 4,5,6,7-tetrabromo-2-azabenzimidazole abolishes CD83 expression in activated Jurkat T cells by interfering with the nucleocytoplasmic translocation of CD83 mRNA. Depletion and knockdown studies demonstrate that the CK2 alpha' subunit is necessary for this regulation, whereas the CK2 a subunit seems to be dispensable. Taken together, the data presented significantly extend our knowledge of the complex regulation of CD83 mRNA processing and provides a novel strategy to interfere with CD83 expression.