Neurofibromin is actively transported to the nucleus.
Mutations in the neurofibromatosis type 1 (NF1) tumor suppressor gene predispose individuals to a variety of benign and malignant tumors. Many tumor suppressors 'shuttle' between the nucleus and the cytoplasm, thus regulating their function. By expressing different NF1 constructs in COS-7 cells (encompassing exons 28-49 and fused to the green fluorescent protein), we identified a functional nuclear localization signal (NLS) in exon 43. Mutation of the NLS completely abolishes the nuclear entry of the NF1-derivative fusion protein. A highly expressed splice variant that lacks this NLS controls the localization and hence the function of neurofibromin. The localization of neurofibromin in the nucleus may provide novel clues to unknown functions for NF1.
Vandenbroucke
Ina
I
Centre for Medical Genetics, Ghent University Hospital, De Pintelaan 185-0K5, 9000 Ghent, Belgium.
Van Oostveldt
Patrick
P
Coene
Elisabeth
E
De Paepe
Anne
A
Messiaen
Ludwine
L
D021581:Active Transport, Cell Nucleus; D017398:Alternative Splicing; D000818:Animals; D019556:COS Cells; D006528:Carcinoma, Hepatocellular / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D049452:Green Fluorescent Proteins; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics; D008164:Luminescent Proteins; D016297:Mutagenesis, Site-Directed; D025542:Neurofibromin 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013347:Subcellular Fractions; D014162:Transfection; D014407:Tumor Cells, Cultured
D008164:Luminescent Proteins; D025542:Neurofibromin 1; D019913:Nuclear Localization Signals; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins