Activation of Stat3 transcription factor by Herpesvirus saimiri STP-A oncoprotein
Activation of Stat3 transcription factor by Herpesvirus saimiri STP-A oncoprotein
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DOI：
10.1128/jvi.78.12.6489-6497.2004
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发表时间：
2004-06-01
影响因子：
5.4
通讯作者：
Jung, JU
中科院分区：
文献类型：
--
作者：
Chung, YH;Cho, NH;Jung, JU
松鼠猴疱疹病毒A亚群株11（STP-A11）的松鼠猴转化蛋白（STP）癌基因不是病毒复制所必需的，但在灵长类动物的培养和淋巴瘤诱导中是淋巴细胞永生化所必需的。我们以前表明，STP-A11通过其SH 2结合基序与细胞Src激酶相互作用，这种相互作用增强Src信号转导。在这里，我们表明，STP-A11相互作用与信号转导和转录激活因子3（Stat 3）独立的Src协会和氨基末端短脯氨酸丰富的基序STP-A11和Stat 3的中央连接区是必要的，它们的相互作用。STP-A11与Src激酶和Stat 3形成三重复合物，其中Src激酶磷酸化Stat 3，导致Stat 3的核定位和转录激活。因此，STP-A11诱导的组成型活性Stat 3引起细胞信号转导，其最终诱导血清剥夺后的细胞存活和增殖。此外，该活性与Fos、细胞周期蛋白D1和Bcl-XL表达的诱导密切相关。这些结果表明，STP-A11独立地靶向两个重要的细胞信号传导分子，Sire和Stat 3，并且这些蛋白质有效地合作以诱导STP-A11介导的转化。
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, Sire and Stat3, and that these proteins cooperate efficiently to induce STP-A11 -mediated transformation.