HIV-1 Vpr induces G2 cell cycle arrest in fission yeast associated with Rad24/14-3-3-dependent, Chk1/Cds1-independent Wee1 upregulation.
Viral protein R (Vpr), an accessory protein of human immunodeficiency virus type 1 (HIV-1), induces the G2 cell cycle arrest in fission yeast for which host factors, such as Wee1 and Rad24, are required. Catalyzing the inhibitory phosphorylation of Cdc2, Wee1 is known to serve as a major regulator of G2/M transition in the eukaryotic cell cycle. It has been reported that the G2 checkpoint induced by DNA damage or incomplete DNA replication is associated with phosphorylation and upregulation of Wee1 for which Chk1 and Cds1 kinase is required. In this study, we demonstrate that the G2 arrest induced by HIV-1 Vpr in fission yeast is also associated with increase in the phosphorylation and amount of Wee1, but in a Chk1/Cds1-independent manner. Rad24 and human 14-3-3 appear to contribute to Vpr-induced G2 arrest by elevating the level of Wee1 expression. It appears that Vpr could cause the G2 arrest through a mechanism similar to, but distinct from, the physiological G2 checkpoint controls. The results may provide useful insights into the mechanism by which HIV-1 Vpr causes the G2 arrest in eukaryotic cells. Vpr may also serve as a useful molecular tool for exploring novel cell cycle control mechanisms.
Matsuda
Naoto
N
Department of Microbiology, Dokkyo Medical University School of Medicine, Kita-kobayashi 880, Mibu, Tochigi 321-0293, Japan.
Tanaka
Hiroko
H
Yamazaki
Sanae
S
Suzuki
Jun-Ichiro
J
Tanaka
Koichi
K
Yamada
Takeshi
T
Masuda
Michiaki
M
D048948:14-3-3 Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism* / Q000502:physiology*; D000071877:Checkpoint Kinase 1; D016195:G2 Phase; D005786:Gene Expression Regulation; D016336:Gene Products, vpr / Q000235:genetics / Q000502:physiology*; D015497:HIV-1; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism* / Q000502:physiology*; D015854:Up-Regulation; D054325:vpr Gene Products, Human Immunodeficiency Virus
D048948:14-3-3 Proteins; D018797:Cell Cycle Proteins; D016336:Gene Products, vpr; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; C501114:rad24 protein, S pombe; D054325:vpr Gene Products, Human Immunodeficiency Virus; D011494:Protein Kinases; C068689:wee1 protein, S pombe; D011505:Protein-Tyrosine Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; C000605873:Chk1 protein, S pombe