在翻译水平调节基因表达对许多生物学过程有着重要意义，因此，生物体内蛋白的翻译活性是由一套严密的机制来调控的。真核细胞翻译启动因子4F(eukaryotic translation initiation factor 4E, elF4E) 是一种帽结合蛋白，其功能是结合mRNA5'末端，与其他翻译启动因子协同作用，开始翻译过程。在帽依赖的翻译调控中，elF4E是一个关键的靶点。elF4E的活性受一个叫做4E结合蛋白（4E-binding protein, 4E-BPs）的阻遏蛋白家族影响。
本文中，研究人员惊奇的发现，高水平的elF4E敲减在翻译活性上引起的变化微乎其微。而进一步的研究表明，随着elF4E表达水平的下降，阻遏蛋白4E-BP1的降解加剧了。在elF4E被敲减的细胞中，能够与elF4E结合的去磷酸化的4E-BP1的降解程度增加了，而高磷酸化的不结合elF4E的4E-BP1没有被降解。研究人员证明KLHL25-CUL3F复合体能够结合去磷酸化的4E-BP1阻遏蛋白，通过泛素化途径将其降解。因此，细胞通过泛素化途径控制了蛋白翻译水平的稳定。（生物谷 Bioon.com ）
doi:10.1016/j.molcel.2012.04.004
PMC:
PMID:
Translational Homeostasis via the mRNA Cap-Binding Protein, eIF4E
Akiko Yanagiya, Eigo Suyama, Hironori Adachi, Yuri V. Svitkin, Pedro Aza-Blanc, Hiroaki Imataka, Satoshi Mikami, Yvan Martineau, Ze'ev A. Ronai, Nahum Sonenberg
Translational control of gene expression plays a key role in many biological processes. Consequently, the activity of the translation apparatus is under tight homeostatic control. eIF4E, the mRNA 5′ cap-binding protein, facilitates cap-dependent translation and is a major target for translational control. eIF4E activity is controlled by a family of repressor proteins, termed 4E-binding proteins (4E-BPs). Here, we describe the surprising finding that despite the importance of eIF4E for translation, a drastic knockdown of eIF4E caused only minor reduction in translation. This conundrum can be explained by the finding that 4E-BP1 is degraded in eIF4E-knockdown cells. Hypophosphorylated 4E-BP1, which binds to eIF4E, is degraded, whereas hyperphosphorylated 4E-BP1 is refractory to degradation. We identified the KLHL25-CUL3 complex as the E3 ubiquitin ligase, which targets hypophosphorylated 4E-BP1. Thus, the activity of eIF4E is under homeostatic control via the regulation of the levels of its repressor protein 4E-BP1 through ubiquitination.
