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

Huidong Yuan, Masakazu Kamata, 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.

H.Y. and M.K. contributed equally to this paper.

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