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Journal of Virology, February 2005, p. 2597-2603, Vol. 79, No. 4
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.4.2597-2603.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Inhibition of Cell Division by the Human Cytomegalovirus IE86 Protein: Role of the p53 Pathway or Cyclin-Dependent Kinase 1/Cyclin B1

Department of Microbiology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa¹

Received 18 June 2004/ Accepted 4 October 2004

The human cytomegalovirus (HCMV) IE86 protein induces the human fibroblast cell cycle from G₀/G₁ to G₁/S, where cell cycle progression stops. Cells with a wild-type, mutated, or null p53 or cells with null p21 protein were transduced with replication-deficient adenoviruses expressing HCMV IE86 protein or cellular p53 or p21. Even though S-phase genes were activated in a p53 wild-type cell, IE86 protein also induced phospho-Ser₁₅ p53 and p21 independent of p14ARF but dependent on ATM kinase. These cells did not enter the S phase. In human p53 mutant, p53 null, or p21 null cells, IE86 protein did not up-regulate p21, cellular DNA synthesis was not inhibited, but cell division was inhibited. Cells accumulated in the G₂/M phase, and there was increased cyclin-dependent kinase 1/cyclin B1 activity. Although the HCMV IE86 protein increases cellular E2F activity, it also blocks cell division in both p53^+/+ and p53^–/– cells.

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