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Journal of Virology, February 1999, p. 1227-1234, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Baculovirus p33 Binds Human p53 and Enhances p53-Mediated Apoptosis

Grigori G. Prikhod'ko,1,dagger Yan Wang,2 Ella Freulich,2 Carol Prives,2 and Lois K. Miller1,*

Departments of Entomology and Genetics, University of Georgia, Athens, Georgia 30602,1 and Department of Biological Sciences, Columbia University, New York, New York 100272

Received 10 August 1998/Accepted 29 October 1998

In vertebrates, p53 participates in numerous biological processes including cell cycle regulation, apoptosis, differentiation, and oncogenic transformation. When insect SF-21 cells were infected with a recombinant of the baculovirus Autographa californica nuclear polyhedrosis virus (AcMNPV) overexpressing human p53, p53 formed a stable complex with the product of the AcMNPV orf92, a novel protein p33. The interaction between p53 and p33 was further confirmed by immunoprecipitation studies. When individually expressed in SF-21 cells, human p53 localized mainly in the nucleus whereas baculovirus p33 displayed diffuse cytoplasmic staining and punctuate nuclear staining. However, coexpression of p33 with p53 resulted in exclusive nuclear localization of p33. In both SF-21 and TN-368 cells, p53 expression induced typical features of apoptosis including nuclear condensation and fragmentation, oligonucleosomal ladder formation, cell surface blebbing, and apoptotic body formation. Coexpression of p53 with a baculovirus inhibitor of apoptosis, p35, OpIAP, or CpIAP, blocked apoptosis, whereas coexpression with p33 enhanced p53-mediated apoptosis approximately twofold. Expression of p53 in SF-21 cells stably expressing OpIAP inhibited cell growth in the presence or absence of p33. Thus, human p53 can influence both insect cell growth and death and baculovirus p33 can modulate the death-inducing effects of p53.

* Corresponding author. Mailing address: Department of Entomology, 413 Biological Sciences, University of Georgia, Athens, GA 30602. Phone: (706) 542-2294. Fax: (706) 542-2279. E-mail: miller{at}arches.uga.edu.

dagger Present address: Molecular Viral Biology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.

Journal of Virology, February 1999, p. 1227-1234, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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