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首页> 外文期刊>Journal of Molecular Biology >Identification and Characterization of the Nuclear Localization/Retention Signal in the EWS Proto-oncoprotein.
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Identification and Characterization of the Nuclear Localization/Retention Signal in the EWS Proto-oncoprotein.

机译：EWS原癌蛋白中核定位/保留信号的鉴定和表征。

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摘要

Ewing sarcoma (EWS) protein, a member of a large family of RNA-binding proteins, contains an N-terminal transcriptional activation domain (EAD) and a C-terminal RNA-binding domain (RBD). Due to its multifunctional properties EWS protein is involved in processes such as gene expression, RNA processing and transport, and cell signaling. Chimeric EWS proteins generated by chromosomal translocations cause malignant tumors. EWS protein is located predominantly in the nucleus, but was found also in the cytosol and associated with the cell membrane. The determinants responsible for the nuclear localization of the protein were as yet unknown. We identified the nuclear localization signal of EWS protein at its C terminus (C-NLS), which is required for the nuclear import and retention of the protein. The C-NLS sequence is conserved in related proto-oncoproteins suggesting an NLS function also in these proteins. Two arginine residues, due to their positive charge, a proline residue and a tyrosine residue are essential for C-NLS function. The nuclear localization of EWS protein is independent of the regions in RBD containing numerous arginine methylation sites, RNA-recognition and zinc finger motifs. Regions in EAD guide the subnuclear partition of EWS protein and contain another but different NLS that allows nucleocytoplasmic shuttling of the N-terminal domain.
机译：尤文氏肉瘤（EWS）蛋白是RNA结合蛋白家族的一员，包含N端转录激活域（EAD）和C端RNA结合域（RBD）。由于EWS蛋白的多功能特性，它参与了基因表达，RNA加工和运输以及细胞信号转导等过程。由染色体易位产生的嵌合EWS蛋白引起恶性肿瘤。 EWS蛋白主要位于细胞核中，但也存在于细胞质中并与细胞膜相关。目前尚不清楚负责蛋白质核定位的决定因素。我们确定了EWS蛋白在其C末端（C-NLS）的核定位信号，这是蛋白质的核导入和保留所必需的。 C-NLS序列在相关的原癌蛋白中是保守的，表明NLS在这些蛋白中也起作用。两个精氨酸残基由于带正电荷，因此脯氨酸残基和酪氨酸残基对于C-NLS功能至关重要。 EWS蛋白的核定位与RBD中包含大量精氨酸甲基化位点，RNA识别和锌指基序的区域无关。 EAD中的区域指导EWS蛋白的亚核分区，并包含另一个但不同的NLS，允许N端结构域发生核质穿梭。

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