title: Identification of a classic nuclear localization signal at the N terminus that regulates the subcellular localization of Rbfox2 isoforms during differentiation of NMuMG and P19 cells.
abstract: Nuclear localization of the alternative splicing factor Rbfox2 is achieved by a C-terminal nuclear localization signal (NLS) which can be excluded from some Rbfox2 isoforms by alternative splicing. While this predicts nuclear and cytoplasmic localization, Rbfox2 is exclusively nuclear in some cell types. Here, we identify a second NLS in the N terminus of Rbfox2 isoform 1A that is not included in Rbfox2 isoform 1F. Rbfox2 1A isoforms lacking the C-terminal NLS are nuclear, whereas equivalent 1F isoforms are cytoplasmic. A shift in Rbfox2 expression toward cytoplasmic 1F isoforms occurs during epithelial to mesenchymal transition (EMT) and could be important in regulating the activity and function of Rbfox2.
authors.affiliation: Institute of Human Genetics, University Medical Center, Johannes Gutenberg University Mainz, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Wenzel
authors.affiliation: Institute of Human Genetics, University Medical Center, Johannes Gutenberg University Mainz, Germany.|Focus Program of Translational Neurosciences, Johannes Gutenberg University Mainz, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schüle
authors.affiliation: Institute of Human Genetics, University Medical Center, Johannes Gutenberg University Mainz, Germany.|Focus Program of Translational Neurosciences, Johannes Gutenberg University Mainz, Germany.
authors.forename: Sonia
authors.initials: S
authors.lastname: Casanovas
authors.affiliation: First Department of Internal Medicine, University Medical Center, Johannes Gutenberg University Mainz, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Strand
authors.affiliation: First Department of Internal Medicine, University Medical Center, Johannes Gutenberg University Mainz, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Strand
authors.affiliation: Institute of Human Genetics, University Medical Center, Johannes Gutenberg University Mainz, Germany.|Focus Program of Translational Neurosciences, Johannes Gutenberg University Mainz, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Winter
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019913:Nuclear Localization Signals / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000072417:Protein Domains; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000072260:RNA Splicing Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D019913:Nuclear Localization Signals; D020033:Protein Isoforms; D000072260:RNA Splicing Factors; C558929:Rbfox2 protein, mouse; D053773:Transforming Growth Factor beta1
keywords: 
  NLS
  ; Rbfox; Rbfox2; cytoplasmic; nuclear; splicing