Increased levels of Wee-1 kinase in G(2) are necessary for Vpr- and gamma irradiation-induced G(2) arrest.
Human immunodeficiency virus type 1 (HIV-1) Vpr induces cell cycle arrest at the G(2)/M transition and subsequently apoptosis. Here we examined the potential involvement of Wee-1 in Vpr-induced G(2) arrest. Wee-1 is a cellular protein kinase that inhibits Cdc2 activity, thereby preventing cells from proceeding through mitosis. We previously showed that the levels of Wee-1 correlate with Vpr-mediated apoptosis. Here, we demonstrate that Vpr-induced G(2) arrest correlated with delayed degradation of Wee-1 at G(2)/M. Experimental depletion of Wee-1 by a small interfering RNA directed to wee-1 mRNA alleviated Vpr-induced G(2) arrest and allowed apparently normal progression through M into G(1). Similar results were observed when cells were arrested at G(2) following gamma irradiation. Thus, Wee-1 is integrally involved as a key cellular regulatory protein in the signal transduction pathway for HIV-1 Vpr-induced cell cycle arrest.
Yuan
Huidong
H
Department of Microbiology, David Geffen School of Medicine, UCLA AIDS Institute, University of California, Los Angeles, CA 90095, USA.
Kamata
Masakazu
M
Xie
Yi-Ming
YM
Chen
Irvin S Y
IS
D016203:CDC2 Protein Kinase / Q000378:metabolism; D018797:Cell Cycle Proteins; D016195:G2 Phase / Q000528:radiation effects*; D005720:Gamma Rays; D016336:Gene Products, vpr / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016196:S Phase; D015398:Signal Transduction; D054325:vpr Gene Products, Human Immunodeficiency Virus
D018797:Cell Cycle Proteins; D016336:Gene Products, vpr; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D054325:vpr Gene Products, Human Immunodeficiency Virus; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human; D016203:CDC2 Protein Kinase