The function of Nup358 in nuclear protein import

Nup358在核蛋白输入中的功能

• 批准号: 31866324
• 负责人: Professor Dr. Ralph Kehlenbach
• 金额: --
• 依托单位: Institut für Molekularbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2006
• 资助国家: 德国
• 起止时间: 2005-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/31866324?language=en
• 关键词: function; Nup358; nuclear; protein; import

Nucleocytoplasmic transport occurs through nuclear pore complexes (NPCs), large structures that are embedded between the inner and outer nuclear membrane. Nucleoporins (the components of the NPC) that localize asymmetrically to either the nuclear or the cytoplasmic side of the NPC have been suggested to function as initial or terminal binding sites for transport complexes. The cytoplasmic nucleoporins Nup214 and Nup358, however, were recently shown to be dispensable for transport of standard import cargoes into the nucleus. In contrast to these findings on standard cargoes, we found two proteins, whose nuclear import is strongly impaired in Nup358-deficient cells. The Rev protein of the human immunodeficiency virus and the cellular protein TERT (telomerase reverse transcriptase) are both nuclear in control cells but largely restricted to the cytoplasm in cells with reduced concentrations of Nup358. We therefore set out to analyze the effect of Nup358-depletion on proteins from a large collection of open reading frames obtained from Dr. Wiemann (DKFZ, Heidelberg). Our preliminary results suggest that about 5-10% of nuclear proteins require Nup358 for efficient nuclear import. Our goals are: a) to identify more Nup358-dependent proteins. b) to characterize the nuclear import pathways of our candidate proteins and to analyze the underlying molecular mechanisms of Nup358-dependent import. c) to analyze potential Nup214- dependent import of proteins.

核质运输通过核孔复合体发生，核孔复合体是嵌入核内和核外核膜之间的大结构。核孔素(NPC的成分)不对称地定位于NPC的核或胞质一侧，已被认为是运输复合体的初始或末端结合位点。然而，细胞质核孔蛋白Nup214和Nup358最近被证明对于标准进口货物进入细胞核的运输是必不可少的。与标准货物上的这些发现相反，我们发现了两种蛋白质，它们的核输入在Nup358缺陷细胞中受到严重损害。人类免疫缺陷病毒的Rev蛋白和细胞蛋白TERT(端粒酶逆转录酶)在对照细胞中都是有核的，但在Nup358浓度降低的细胞中主要局限于细胞质。因此，我们开始分析Nup358-耗尽对从Wiemann博士(DKFZ，Heidelberg)获得的大量开放阅读框中蛋白质的影响。我们的初步结果表明，大约5%-10%的核蛋白需要Nup358才能有效地进行核进口。我们的目标是：a)鉴定更多依赖Nup358的蛋白质。B)表征我们候选蛋白质的核进口途径，并分析Nup358依赖的进口的潜在分子机制。C)分析可能依赖Nup214的蛋白质进口。