Competition between nuclear localization and secretory signals determines the subcellular fate of a single CUG-initiated form of FGF3

Kiefer, P., Acland, P., Pappin, D., Peters, G., Dickson, C. (September 1994) Competition between nuclear localization and secretory signals determines the subcellular fate of a single CUG-initiated form of FGF3. EMBO J, 13 (17). pp. 4126-36. ISSN 0261-4189 (Print)0261-4189 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/8076608

Abstract

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.

Item Type: Paper
Uncontrolled Keywords: Amino Acid Sequence Animals Base Sequence Biological Transport/genetics Cell Compartmentation Cell Nucleolus/metabolism Cell Nucleus/ metabolism Fibroblast Growth Factor 3 Fibroblast Growth Factors/genetics/isolation & purification/ metabolism/secretion Fluorescent Antibody Technique Mice Molecular Sequence Data Open Reading Frames Peptide Chain Initiation, Translational Protein Biosynthesis Protein Processing, Post-Translational Proto-Oncogene Proteins/genetics/isolation & purification/ metabolism/secretion Structure-Activity Relationship
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > fibroblast growth factor
CSHL Authors:
Communities: CSHL labs > Pappin lab
Depositing User: Matt Covey
Date: 1 September 1994
Date Deposited: 18 Sep 2014 19:28
Last Modified: 18 Sep 2014 19:28
PMCID: PMC395335
URI: http://repository.cshl.edu/id/eprint/30747

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