在翻譯水平調(diào)節(jié)基因表達(dá)對(duì)許多生物學(xué)過(guò)程有著重要意義,，因此,，生物體內(nèi)蛋白的翻譯活性是由一套嚴(yán)密的機(jī)制來(lái)調(diào)控的,。真核細(xì)胞翻譯啟動(dòng)因子4F(eukaryotic translation initiation factor 4E, elF4E) 是一種帽結(jié)合蛋白,，其功能是結(jié)合mRNA5'末端,，與其他翻譯啟動(dòng)因子協(xié)同作用,，開始翻譯過(guò)程,。在帽依賴的翻譯調(diào)控中，elF4E是一個(gè)關(guān)鍵的靶點(diǎn),。elF4E的活性受一個(gè)叫做4E結(jié)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(xiàn),，高水平的elF4E敲減在翻譯活性上引起的變化微乎其微,。而進(jìn)一步的研究表明，隨著elF4E表達(dá)水平的下降,，阻遏蛋白4E-BP1的降解加劇了,。在elF4E被敲減的細(xì)胞中，能夠與elF4E結(jié)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(jié)合elF4E的4E-BP1沒有被降解,。研究人員證明KLHL25-CUL3F復(fù)合體能夠結(jié)合去磷酸化的4E-BP1阻遏蛋白，通過(guò)泛素化途徑將其降解,。因此,，細(xì)胞通過(guò)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.
