title: Mutational analysis of growth arrest and cellular localization of human immunodeficiency virus type 1 Vpr in the budding yeast, Saccharomyces cerevisiae.
abstract: Viral protein R (Vpr), one of the accessory gene products of human immunodeficiency virus type 1 (HIV-1), is responsible for the incorporation of a viral genome into the nucleus upon infection. Vpr also arrests the cell cycle and induces apoptosis in infected cells. Similarly, in yeast, Vpr localizes in the nucleus and shows growth inhibitory activity; however, the molecular mechanism of growth inhibition remains unknown. To elucidate this mechanism, several point mutations of Vpr, which are known to perturb several phenotypes of Vpr in mammalian cells, were introduced in the budding yeast, Saccharomyces cerevisiae. For the first time, we found that growth inhibition by Vpr occurred independently of intracellular localization in yeast, as has previously been reported in mammals. We also identified several amino acid residues, the mutation of which cancels growth inhibitory activity, and/or alters localization, both in yeast and mammalian cells, suggesting the importance of these residues for the phenotypes.
authors.affiliation: Antibiotics Laboratory, Discovery Research Institute, RIKEN, Wako, Saitama, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Nakazawa
authors.forename: Nobumoto
authors.initials: N
authors.lastname: Watanabe
authors.forename: Masaya
authors.initials: M
authors.lastname: Imoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Osada
mesh_terms: D016336:Gene Products, vpr / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015497:HIV-1 / Q000737:chemistry*; D017354:Point Mutation; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000378:metabolism*; D014170:Transformation, Genetic; D054325:vpr Gene Products, Human Immunodeficiency Virus
chemical_list: D016336:Gene Products, vpr; D054325:vpr Gene Products, Human Immunodeficiency Virus