Evidence for specific nucleocytoplasmic transport pathways used by leucine-rich nuclear export signals

作     者：Elfgang, C Rosorius, O Hofer, L Jaksche, H Hauber, J Bevec, D 

作者机构：Novartis Res Inst Dept Immunol A-1235 Vienna Austria Univ Erlangen Nurnberg Inst Clin & Mol Virol D-91054 Erlangen Germany 

出 版 物：《PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA》 (美国国家科学院汇刊)

年 卷 期：1999年第96卷第11期

页      面：6229-6234页

核心收录：

学科分类：07[理学] 08[工学] 

主　　题：氨基酸序列 载体蛋白质类/拮抗剂和抑制剂 载体蛋白质类/化学 载体蛋白质类/代谢 细胞核/代谢 克隆 分子 细胞质/代谢 基因产物 rev/代谢 谷胱甘肽转移酶/代谢 HIV-1/生理学 HeLa细胞 人类嗜T淋巴细胞病毒1型/生理学 核胞浆转运蛋白类 亮氨酸 微量注射 模型 生物学 分子序列数据 核蛋白质类/代谢 肽起始因子类/代谢 RNA结合蛋白质类 受体 胞质和核 重组融合蛋白质类/代谢 信号传导 rev基因产物 人免疫缺陷病毒 人类 

摘      要：Various proteins with different biological activities have been observed to be translocated from the nucleus to the cytoplasm in an energy- and signal-dependent manner in eukaryotic cells. This nuclear export is directed by nuclear export signals (NESs), typically characterized by hydrophobic, primarily leucine, amino acid residues. Moreover, it has been shown that CRM1/exportin I is an export receptor for leucine-rich NESs. However, additional NES-interacting proteins have been described. In particular, eukaryotic initiation factor 5A (eIF-5A) has been shown to be a critical cellular cofactor for the nuclear export of the HIV type 1 (HIV-I) Rev trans-activator protein. In this study we compared the nuclear export activity of NESs of different origin. Microinjection of export substrates into the nucleus of somatic cells in combination with specific inhibitors indicated that specific nuclear export pathways exist for different NES-containing proteins. In particular, inhibition of eIF-5A blocked the nuclear export of NESs derived from the HIV-1 Rev and human T cell leukemia virus type I Rex transactivators, whereas nucleocytoplasmic translocation of the protein kinase inhibitor-NES was unaffected. In contrast, however, inhibition of CRM/exportin 1 blocked the nuclear export of all NES-containing proteins investigated. Our data confirm that CRM1/exportin 1 is a general export receptor for leucine-rich NESs and suggest that eIF-5A acts either upstream of CRM1/exportin 1 or forms a complex with the NES and CRM1/exportin 1 in the nucleocytoplasmic translocation of the HIV-1 Rev and human T cell leukemia virus type I Rex RNA export factors.