在翻譯水平調節(jié)基因表達對許多生物學過程有著重要意義,，因此，生物體內蛋白的翻譯活性是由一套嚴密的機制來調控的,。真核細胞翻譯啟動因子4F(eukaryotic translation initiation factor 4E, elF4E) 是一種帽結合蛋白,，其功能是結合mRNA5'末端，與其他翻譯啟動因子協(xié)同作用,，開始翻譯過程,。在帽依賴的翻譯調控中，elF4E是一個關鍵的靶點,。elF4E的活性受一個叫做4E結合蛋白（4E-binding protein, 4E-BPs）的阻遏蛋白家族影響,。
本文中，研究人員驚奇的發(fā)現,，高水平的elF4E敲減在翻譯活性上引起的變化微乎其微,。而進一步的研究表明，隨著elF4E表達水平的下降,，阻遏蛋白4E-BP1的降解加劇了,。在elF4E被敲減的細胞中，能夠與elF4E結合的去磷酸化的4E-BP1的降解程度增加了,，而高磷酸化的不結合elF4E的4E-BP1沒有被降解,。研究人員證明KLHL25-CUL3F復合體能夠結合去磷酸化的4E-BP1阻遏蛋白，通過泛素化途徑將其降解,。因此,，細胞通過泛素化途徑控制了蛋白翻譯水平的穩(wěn)定。（生物谷 Bioon.com ）
doi:10.1016/j.molcel.2012.04.004
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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.
