Depletion of Wee-1 kinase is necessary for both human immunodeficiency virus type 1 Vpr- and gamma irradiation-induced apoptosis.
Human immunodeficiency virus (HIV) protein R (Vpr) induces G2 arrest, and prolonged G2 arrest leads to apoptosis. We find that in HeLa cells the cell cycle regulatory kinase, Wee-1, is depleted following prolonged G2 arrest induced by Vpr. Of note, small interfering RNAs directed to Wee-1 triggered apoptosis, suggesting a direct role for Wee-1 in apoptosis. In support of this hypothesis, overexpression of Wee-1 suppressed Vpr-mediated apoptosis. Importantly, similar results were observed with cells induced to undergo apoptosis gamma irradiation. Thus, Wee-1 may serve as a key regulator of both HIV type 1 Vpr- and gamma irradiation-mediated apoptosis and possibly serve as a general regulator linking the cell cycle to some pathways of apoptosis.
Yuan
Huidong
H
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California 90095, USA.
Xie
Yi-Ming
YM
Chen
Irvin S Y
IS
D017209:Apoptosis / Q000528:radiation effects; D018797:Cell Cycle Proteins; D005720:Gamma Rays; D016336:Gene Products, vpr / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D054325:vpr Gene Products, Human Immunodeficiency Virus
D018797:Cell Cycle Proteins; D016336:Gene Products, vpr; D009687:Nuclear Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human