Genetic studies with the fission yeast Schizosaccharomyces pombe suggest involvement of wee1, ppa2, and rad24 in induction of cell cycle arrest by human immunodeficiency virus type 1 Vpr.
Accessory protein Vpr of human immunodeficiency virus type 1 (HIV-1) arrests cell cycling at G(2)/M phase in human and simian cells. Recently, it has been shown that Vpr also causes cell cycle arrest in the fission yeast Schizosaccharomyces pombe, which shares the cell cycle regulatory mechanisms with higher eukaryotes including humans. In this study, in order to identify host cellular factors involved in Vpr-induced cell cycle arrest, the ability of Vpr to cause elongated cellular morphology (cdc phenotype) typical of G(2)/M cell cycle arrest in wild-type and various mutant strains of S. pombe was examined. Our results indicated that Vpr caused the cdc phenotype in wild-type S. pombe as well as in strains carrying mutations, such as the cdc2-3w, Deltacdc25, rad1-1, Deltachk1, Deltamik1, and Deltappa1 strains. However, other mutants, such as the cdc2-1w, Deltawee1, Deltappa2, and Deltarad24 strains, failed to show a distinct cdc phenotype in response to Vpr expression. Results of these genetic studies suggested that Wee1, Ppa2, and Rad24 might be required for induction of cell cycle arrest by HIV-1 Vpr. Cell proliferation was inhibited by Vpr expression in all of the strains examined including the ones that did not show the cdc phenotype. The results supported the previously suggested possibility that Vpr affects the cell cycle and cell proliferation through different pathways.
Masuda
M
M
Department of Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan. mmasuda@m.u-tokyo.ac.jp
Nagai
Y
Y
Oshima
N
N
Tanaka
K
K
Murakami
H
H
Igarashi
H
H
Okayama
H
H
D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D016195:G2 Phase; D016336:Gene Products, vpr / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008938:Mitosis; D016296:Mutagenesis; D009687:Nuclear Proteins; D010641:Phenotype; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins; D020666:ras-GRF1 / Q000235:genetics / Q000378:metabolism; D054325:vpr Gene Products, Human Immunodeficiency Virus
D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D016336:Gene Products, vpr; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; C501114:rad24 protein, S pombe; D020666:ras-GRF1; D054325:vpr Gene Products, Human Immunodeficiency Virus; C068689:wee1 protein, S pombe; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human; D010749:Phosphoprotein Phosphatases