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Journal of Virology, June 2004, p. 6489-6497, Vol. 78, No. 12
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.12.6489-6497.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Activation of Stat3 Transcription Factor by Herpesvirus Saimiri STP-A Oncoprotein

Young-Hwa Chung,1,2 Nam-hyuk Cho,1 Maria Ines Garcia,1 Sun-Hwa Lee,1 Pinghui Feng,1 and Jae U. Jung1*

Department of Microbiology and Molecular Genetics and Tumor Virology Division, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772-9102,1 School of Nanoscience and Technology, Pusan National University, Pusan, South Korea2

Received 17 November 2003/ Accepted 16 February 2004

The saimiri transforming protein (STP) oncogene of Herpesvirus saimiri subgroup A strain 11 (STP-A11) is not required for viral replication but is required for lymphoid cell immortalization in culture and lymphoma induction in primates. We previously showed that STP-A11 interacts with cellular Src kinase through its SH2 binding motif and that this interaction elicits Src signal transduction. Here we demonstrate that STP-A11 interacts with signal transducer and activator of transcription 3 (Stat3) independently of Src association and that the amino-terminal short proline-rich motif of STP-A11 and the central linker region of Stat3 are necessary for their interaction. STP-A11 formed a triple complex with Src kinase and Stat3 where Src kinase phosphorylated Stat3, resulting in the nuclear localization and transcriptional activation of Stat3. Consequently, the constitutively active Stat3 induced by STP-A11 elicited cellular signal transduction, which ultimately induced cell survival and proliferation upon serum deprivation. Furthermore, this activity was strongly correlated with the induction of Fos, cyclin D1, and Bcl-XL expression. These results demonstrate that STP-A11 independently targets two important cellular signaling molecules, Src and Stat3, and that these proteins cooperate efficiently to induce STP-A11-mediated transformation.

* Corresponding author. Mailing address: Tumor Virology Division, New England Primate Research Center, Harvard Medical School, P.O. Box 9102, 1 Pine Hill Dr., Southborough, MA 01772-9102. Phone: (508) 624-8083. Fax: (508) 786-1416. E-mail: jae_jung{at}hms.harvard.edu.

Journal of Virology, June 2004, p. 6489-6497, Vol. 78, No. 12
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.12.6489-6497.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Garcia, M. I., Kaserman, J., Chung, Y.-H., Jung, J. U., Lee, S.-H. (2007). Herpesvirus Saimiri STP-A Oncoprotein Utilizes Src Family Protein Tyrosine Kinase and Tumor Necrosis Factor Receptor-Associated Factors To Elicit Cellular Signal Transduction. J. Virol. 81: 2663-2674 [Abstract] [Full Text]  
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