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Molecular and Cellular Biology, March 2003, p. 1885-1895, Vol. 23, No. 6
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.6.1885-1895.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Human Cytomegalovirus pp71 Stimulates Cell Cycle Progression by Inducing the Proteasome-Dependent Degradation of the Retinoblastoma Family of Tumor Suppressors

Robert F. Kalejta, Jill T. Bechtel,{dagger} and Thomas Shenk*

Molecular Biology Department, Princeton University, Princeton, New Jersey 08544-1014

Received 31 October 2002/ Returned for modification 2 December 2002/ Accepted 6 December 2002

The oncoproteins of the DNA tumor viruses, adenovirus E1A, simian virus 40 T antigen, and papillomavirus E7, each interact with the retinoblastoma family of tumor suppressors, leading to cell cycle stimulation, apoptosis induction, and cellular transformation. These proteins utilize a conserved LXCXE motif, which is also found in cellular proteins, to target the retinoblastoma family. Here, we describe a herpesvirus protein that shares a subset of the properties of the DNA tumor virus oncoproteins but maintains important differences as well. The human cytomegalovirus pp71 protein employs an LXCXD motif to attack the retinoblastoma family members and induce DNA synthesis in quiescent cells. pp71 binds to and induces the degradation of the hypophosphorylated forms of the retinoblastoma protein and its family members p107 and p130 in a proteasome-dependent manner. However, pp71 does not induce apoptosis and fails to transform cells. Thus, the similarities and differences in comparison to E1A, T antigen, and E7 make pp71 an interesting new tool with which to further dissect the role of the retinoblastoma/E2F pathway in cellular growth control and carcinogenesis.

* Corresponding author. Mailing address: Molecular Biology Department, Princeton University, Princeton, NJ 08544-1014. Phone: (609) 258-5992. Fax: (609) 258-1704. E-mail: tshenk{at}molbio.princeton.edu.

{dagger} Present address: Department of Microbiology, Immunology, and Medicine, University of California Medical Center, San Francisco, Calif.

Molecular and Cellular Biology, March 2003, p. 1885-1895, Vol. 23, No. 6
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.6.1885-1895.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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