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Journal of Virology, August 2004, p. 8183-8190, Vol. 78, No. 15
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.15.8183-8190.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Increased Levels of Wee-1 Kinase in G2 Are Necessary for Vpr- and Gamma Irradiation-Induced G2 Arrest

Huidong Yuan,{dagger} Masakazu Kamata,{dagger} Yi-Ming Xie, and Irvin S. Y. Chen*

Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, UCLA AIDS Institute, University of California, Los Angeles, California 90095

Received 25 November 2003/ Accepted 18 March 2004

Human immunodeficiency virus type 1 (HIV-1) Vpr induces cell cycle arrest at the G2/M transition and subsequently apoptosis. Here we examined the potential involvement of Wee-1 in Vpr-induced G2 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 G2 arrest correlated with delayed degradation of Wee-1 at G2/M. Experimental depletion of Wee-1 by a small interfering RNA directed to wee-1 mRNA alleviated Vpr-induced G2 arrest and allowed apparently normal progression through M into G1. Similar results were observed when cells were arrested at G2 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.

* Corresponding author. Mailing address: Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, UCLA AIDS Institute, University of California, Los Angeles, CA 90095. Phone: (310) 825-4793. Fax: (310) 794-7682. E-mail: syuchen{at}mednet.ucla.edu.

{dagger} H.Y. and M.K. contributed equally to this paper.

Journal of Virology, August 2004, p. 8183-8190, Vol. 78, No. 15
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.15.8183-8190.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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