Lee Sun Kyung, Lee Ji Sun, Shin Ki Soon, Yoo Soon Ji
Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Korea.
Mol Cells. 2007 Dec 31;24(3):445-51.
Translation initiation factor 4E (eIF4E) is a key regulator of protein synthesis. Abnormal regulation of eIF4E is closely linked to oncogenic transformation. Several regulatory mechanisms affecting eIF4E are discussed, including transcriptional regulation, phosphorylation and binding of an inhibitor protein. However it is not clear how the level of eIF4E protein is regulated under basal conditions. Here we demonstrate that Diap1 (Drosophila Inhibitor of Apoptosis Protein), a cell death inhibitor, binds directly to eIF4E and poly-ubiquitinates it via its E3 ligase activity, promoting its proteasome-dependent degradation. Expression of Diap1 caused a reduction of Cyclin D1 protein level and inhibited the growth stimulation induced by overexpression of eIF4E. Taken together, our results suggest that the level of eIF4E protein is regulated by Diap1, and that IAPs may play a role in cap-dependent translation by regulating the level of eIF4E protein.
翻译起始因子4E（eIF4E）是蛋白质合成的关键调节因子。eIF4E的异常调节与致癌转化密切相关。本文讨论了影响eIF4E的几种调节机制，包括转录调节、磷酸化以及与一种抑制蛋白的结合。然而，目前尚不清楚在基础条件下eIF4E蛋白水平是如何调节的。在这里，我们证明了凋亡抑制蛋白Diap1（果蝇凋亡抑制蛋白）通过其E3连接酶活性直接与eIF4E结合并使其多聚泛素化，促进其蛋白酶体依赖性降解。Diap1的表达导致细胞周期蛋白D1蛋白水平降低，并抑制了由eIF4E过表达诱导的生长刺激。综上所述，我们的结果表明eIF4E蛋白水平受Diap1调节，并且IAPs可能通过调节eIF4E蛋白水平在帽依赖性翻译中发挥作用。
