title: Ste11p, a high-mobility-group box DNA-binding protein, undergoes pheromone- and nutrient-regulated nuclear-cytoplasmic shuttling.
abstract: The high-mobility-group (HMG) box is a conserved DNA-binding domain found in a family of transcription factors that regulate growth and development. One family member, Ste11p, directs sexual differentiation of Schizosaccharomyces pombe by binding specific DNA sequences upstream of genes required for mating and meiosis. Here, we show that Ste11p is a shuttling protein. In growing cells, Ste11p is present in low levels and is pancellular. Mating pheromones and nutrient limitation trigger nuclear accumulation and increased expression of the transcription factor. Several mechanisms likely control Ste11p localization. First, the 14-3-3 protein, Rad24p, binds phosphorylated Ste11p and inhibits its nuclear accumulation. Second, the HMG domain of Ste11p contains a basic cluster nuclear localization signal. Finally, treatment of cells with leptomycin B, an exportin inhibitor, results in the nuclear accumulation of Ste11p. A Ste11p deletion mutation, DeltaC54, mimics the effects of leptomycin B. The C54 region contains no identifiable nuclear export signal but instead is required for biological activity and to stimulate Ste11p target gene expression. These results provide evidence that both nuclear import and export mechanisms operate to regulate cellular localization of an HMG box protein. In addition, they establish a paradigm for the potential role of pheromone/hormone-like polypeptides in cellular localization of this important class of developmental regulators.
authors.affiliation: Department of Microbiology and Immunology, Morse Institute for Molecular Genetics, and Program in Molecular and Cellular Biology, State University of New York Downstate Medical Center, Brooklyn, New York 11203-2098, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Qin
authors.forename: Wenfei
authors.initials: W
authors.lastname: Kang
authors.forename: Betty
authors.initials: B
authors.lastname: Leung
authors.forename: Maureen
authors.initials: M
authors.lastname: McLeod
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D003227:Conjugation, Genetic; D003470:Culture Media; D003593:Cytoplasm / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins; D015966:Gene Expression Regulation, Fungal; D049452:Green Fluorescent Proteins; D024742:HMG-Box Domains; D047908:Intracellular Signaling Peptides and Proteins; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D009584:Nitrogen / Q000378:metabolism; D019913:Nuclear Localization Signals; D010675:Pheromones / Q000378:metabolism*; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000097606:Exportin 1 Protein
chemical_list: D018797:Cell Cycle Proteins; D003470:Culture Media; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D049452:Green Fluorescent Proteins; D047908:Intracellular Signaling Peptides and Proteins; D028884:Karyopherins; D008164:Luminescent Proteins; D009584:Nitrogen; D019913:Nuclear Localization Signals; D010675:Pheromones; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; D000097606:Exportin 1 Protein; C103266:PAT1 protein, S cerevisiae; C085847:map2 protein, S pombe; C501114:rad24 protein, S pombe; C071596:ste11 protein, S pombe