Activation of Stat3 transcription factor by Herpesvirus saimiri STP-A oncoprotein.

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.
Mesh Terms:
Animals, COS Cells, Cell Line, Cell Transformation, Viral, DNA-Binding Proteins, Herpesvirus 2, Saimiriine, Humans, Mice, NIH 3T3 Cells, Oncogene Proteins, Viral, Phosphotransferases, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, STAT3 Transcription Factor, Signal Transduction, Trans-Activators, Transcriptional Activation, Transfection
J. Virol.
Date: Jun. 01, 2004
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