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TCP/ILF3蛋白两种剪接异构体的细胞周期依赖性细胞内分布

Cell cycle dependent intracellular distribution of two spliced isoforms of TCP/ILF3 proteins.

作者信息

Xu You Hai, Leonova Tatyana, Grabowski Gregory A

机构信息

The Children's Hospital Research Foundation, Division of Human Genetics, Cincinnati, OH 45229-3039, USA.

出版信息

Mol Genet Metab. 2003 Dec;80(4):426-36. doi: 10.1016/j.ymgme.2003.09.006.

DOI:10.1016/j.ymgme.2003.09.006
PMID:14654356
Abstract

TCP80 is an approximately 80kDa mammalian cytoplasmic protein that binds to a set of mRNAs and inhibits their translation in vitro and ex vivo. This protein has high sequence similarity to interleukin-2 enhancer-binding factors (NF90/ILF3) and the M-phase phosphoprotein (MPP4)/DRBP76. A 110kDa immunologic isoform of TCP80/NF90/MPP4/DRBP76, termed TCP110, also is present in cytoplasm and nuclei of many types of cells. A cDNA sequence coding for TCP110 was derived by 5(')RACE. The TCP110 sequence is identical to ILF3. The gene coding for TCP110/ILF3 mapped to human chromosome 19 and the gene organization was analyzed using TCP80 and TCP110/ILF3 cDNA sequences. The TCP/ILF3 gene spans >34.8kb and contains 21 exons. At least one alternatively spliced product involving exons 19-21 exists and predicts the formation of either TCP80 or TCP110/ILF3. However, the functional relationships of TCP80 and TCP110/ILF3 required elucidation. The metabolic turnover rates and subcellular distribution of TCP80 and TCP110/ILF3 during the cell cycle showed TCP80 to be relatively stable (t(1/2)=5 days) in the cytoplasmic compartment. In comparison, TCP110/ILF3 migrated between the cytoplasmic and nuclear compartments during the cell cycle. The TCP110 C-terminal segment contains an additional nuclear localizing signal that plays a role in its nuclear translocation. This study indicates that the multiple cellular functions, i.e., translation control, interleukin-2 enhancer binding, or cell division, of TCP/ILF3 are fulfilled by alternatively spliced isoforms.

摘要

TCP80是一种分子量约为80kDa的哺乳动物细胞质蛋白,它能与一组mRNA结合,并在体外和体内抑制其翻译。该蛋白与白细胞介素-2增强子结合因子(NF90/ILF3)和M期磷蛋白(MPP4)/DRBP76具有高度的序列相似性。TCP80/NF90/MPP4/DRBP76的一种110kDa免疫异构体,称为TCP110,也存在于多种类型细胞的细胞质和细胞核中。通过5(')RACE获得了编码TCP110的cDNA序列。TCP110序列与ILF3相同。编码TCP110/ILF3的基因定位于人类染色体19,并使用TCP80和TCP110/ILF3 cDNA序列分析了基因结构。TCP/ILF3基因跨度大于34.8kb,包含21个外显子。至少存在一种涉及外显子19 - 21的可变剪接产物,可预测形成TCP80或TCP110/ILF3。然而,TCP80和TCP110/ILF3的功能关系需要阐明。细胞周期中TCP80和TCP110/ILF3的代谢周转率和亚细胞分布表明,TCP80在细胞质区室中相对稳定(半衰期=5天)。相比之下,TCP110/ILF3在细胞周期中在细胞质和细胞核区室之间迁移。TCP110的C末端片段包含一个额外的核定位信号,该信号在其核转位中起作用。这项研究表明,TCP/ILF3的多种细胞功能,即翻译控制、白细胞介素-2增强子结合或细胞分裂,是由可变剪接异构体实现的。

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