COMPETITION BETWEEN NUCLEAR-LOCALIZATION AND SECRETORY SIGNALS DETERMINES THE SUBCELLULAR FATE OF A SINGLE CUG-INITIATED FORM OF FGF3
COMPETITION BETWEEN NUCLEAR-LOCALIZATION AND SECRETORY SIGNALS DETERMINES THE SUBCELLULAR FATE OF A SINGLE CUG-INITIATED FORM OF FGF3
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DOI：
10.1002/j.1460-2075.1994.tb06730.x
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发表时间：
1994-09-01
期刊：
影响因子：
11.4
通讯作者：
DICKSON, C
中科院分区：
文献类型：
--
作者：
KIEFER, P;ACLAND, P;DICKSON, C
小鼠FGF 3的假定开放阅读框，起始于最5 'AUG密码子，预测了用于分泌的信号肽的疏水性N-末端特征。然而，在网织红细胞裂解物和转染的COS-1细胞中，全长Fgf-3 cDNA几乎完全从上游CUG密码子翻译。所产生的产物分布在细胞核和分泌途径中，这意味着单一CUG起始形式的FGF3具有双重命运。通过分析一系列的缺失和替换突变体，并通过连接部分FGF3的异源蛋白，我们表明，分泌介导的裂解相邻的先前定义的信号肽，而核定位主要是由一个经典的，但相对较弱的二分基序。在FGF3的情况下，核定位还需要位于信号肽上游的N-末端序列。因此，FGF3的亚细胞命运是由相同蛋白质内分泌和核定位信号的竞争效应决定的，而不是由替代的起始或加工决定的。
The presumed open reading frame for mouse FGF3, starting at the most 5' AUG codon, predicts a hydrophobic N-terminus characteristic of a signal peptide for secretion. However, in reticulocyte lysates and transfected COS-1 cells, the full-length Fgf-3 cDNA is translated almost exclusively from an upstream CUG codon. The resultant products are distributed in both the nucleus and the secretory pathway, implying that the single CUG-initiated form of FGF3 has dual fates. By analysing a series of deletion and replacement mutants and by linking parts of FGF3 to a heterologous protein, we show that secretion is mediated by cleavage adjacent to the previously defined signal peptide, whereas nuclear localization is determined primarily by a classical but relatively weak bipartite motif. In the context of FGF3, nuclear localization also requires the N-terminal sequences which lie upstream of the signal peptide. Thus, the subcellular fate of FGF3 is determined by the competing effects of signals for secretion and nuclear localization within the same protein, rather than by alternative initiation or processing.