Pyronnet S, Dostie J, Sonenberg N
Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec H3G 1Y6, Canada.
Genes Dev. 2001 Aug 15;15(16):2083-93. doi: 10.1101/gad.889201.
Cap-dependent translation is mediated by eIF4F, a protein complex composed of three subunits as follows: eIF4E, which recognizes the mRNA 5' cap structure; eIF4A, an RNA-helicase; and eIF4G, a scaffolding protein that binds eIF4E, eIF4A, and the eIF4E-kinase Mnk1 simultaneously. eIF4E is hypophosphorylated and cap-dependent translation is reduced at mitosis. Here, we show that 4E-BP1, a suppressor of eIF4E function, is also hypophosphorylated in mitosis, resulting in disruption of the eIF4F complex. Consequently, eIF4E is sequestered from the eIF4G/Mnk1 complex. These results explain the specific inhibition of cap-dependent translation in mitosis and also explain how eIF4E is rendered hypophosphorylated during mitosis. Furthermore, eIF4E interaction with eIF4GII is strongly decreased coincident with hyperphosphorylation of eIF4GII. Thus, inhibition of cap-dependent translation in mitosis results from a combination of phosphorylation modifications leading to eIF4F complex disruption.
帽依赖性翻译由eIF4F介导，eIF4F是一种由三个亚基组成的蛋白质复合物，具体如下：eIF4E，识别mRNA 5'帽结构；eIF4A，一种RNA解旋酶；以及eIF4G，一种支架蛋白，可同时结合eIF4E、eIF4A和eIF4E激酶Mnk1。eIF4E在有丝分裂时发生低磷酸化，帽依赖性翻译减少。在此，我们表明，作为eIF4E功能抑制剂的4E-BP1在有丝分裂时也发生低磷酸化，导致eIF4F复合物的破坏。因此，eIF4E被从eIF4G/Mnk1复合物中隔离出来。这些结果解释了有丝分裂中帽依赖性翻译的特异性抑制，也解释了eIF4E在有丝分裂期间如何发生低磷酸化。此外，随着eIF4GII的过度磷酸化，eIF4E与eIF4GII的相互作用强烈减少。因此，有丝分裂中帽依赖性翻译的抑制是由导致eIF4F复合物破坏的磷酸化修饰组合引起的。
