Merrick William C
From the Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4935
J Biol Chem. 2015 Oct 2;290(40):24091-9. doi: 10.1074/jbc.R115.675280. Epub 2015 Aug 31.
The original purification of the heterotrimeric eIF4F was published over 30 years ago (Grifo, J. A., Tahara, S. M., Morgan, M. A., Shatkin, A. J., and Merrick, W. C. (1983) J. Biol. Chem. 258, 5804-5810). Since that time, numerous studies have been performed with the three proteins specifically required for the translation initiation of natural mRNAs, eIF4A, eIF4B, and eIF4F. These have involved enzymatic and structural studies of the proteins and a number of site-directed mutagenesis studies. The regulation of translation exhibited through the mammalian target of rapamycin (mTOR) pathway is predominately seen as the phosphorylation of 4E-BP, an inhibitor of protein synthesis that functions by binding to the cap binding subunit of eIF4F (eIF4E). A hypothesis that requires the disassembly of eIF4F during translation initiation to yield free subunits (eIF4A, eIF4E, and eIF4G) is presented.
异源三聚体eIF4F的原始纯化方法在30多年前就已发表(Grifo, J. A., Tahara, S. M., Morgan, M. A., Shatkin, A. J., and Merrick, W. C. (1983) J. Biol. Chem. 258, 5804 - 5810)。从那时起,人们对天然mRNA翻译起始特别需要的三种蛋白质eIF4A、eIF4B和eIF4F进行了大量研究。这些研究包括对这些蛋白质的酶学和结构研究以及一些定点诱变研究。通过雷帕霉素哺乳动物靶标(mTOR)途径表现出的翻译调控主要表现为4E - BP的磷酸化,4E - BP是一种蛋白质合成抑制剂,通过与eIF4F的帽结合亚基(eIF4E)结合发挥作用。本文提出了一种假说,即在翻译起始过程中需要eIF4F解体以产生游离亚基(eIF4A、eIF4E和eIF4G)。