STAT3 beta, a splice variant of transcription factor STAT3, is a dominant negative regulator of transcription
STAT3 beta, a splice variant of transcription factor STAT3, is a dominant negative regulator of transcription
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DOI：
10.1074/jbc.271.22.13221
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发表时间：
1996-05-31
影响因子：
4.8
通讯作者：
deGroot, RP
中科院分区：
文献类型：
--
作者：
Caldenhoven, E;vanDijk, TB;deGroot, RP
89-kDa的STAT 3蛋白是一种潜在的转录因子，其响应于细胞因子（白细胞介素（IL）-5和-6）和生长因子（表皮生长因子）而被激活。IL-5与其特异性受体的结合激活JAK 2，这导致STAT 3蛋白的酪氨酸磷酸化。在这里，我们报告的cDNA编码的变体的转录因子STAT 3（命名为STAT 3 β），这是通过筛选嗜酸性粒细胞的cDNA文库中分离的克隆。与野生型STAT 3相比，STAT 3 β缺乏位于C末端附近的50个碱基对的内部结构域。这种剪接产物是STAT 3的天然存在的同种型，并编码80-kDa蛋白。我们通过在COS细胞中重建人IL-5 R发现，与STAT 3一样，STAT 3 β在酪氨酸上磷酸化，并在IL-5刺激后与ICAM-1启动子的pIRE结合。然而，在瞬时转染测定中，STAT 3 β不能激活含有pIRE的启动子。相反，STAT 3 β的共表达抑制了STAT 3的反式激活潜力。这些结果表明，STAT 3 β作为转录的负调节因子发挥作用。
The 89-kDa STAT3 protein is a latent transcription factor which is activated in response to cytokines (interleukin (IL)-5 and -6) and growth factors (epidermal growth factor). Binding of IL-5 to its specific receptor activates JAK2 which leads to the tyrosine phosphorylation of STAT3 proteins. Here we report the cloning of a cDNA encoding a variant of the transcription factor STAT3 (named STAT3 beta) which was isolated by screening an eosinophil cDNA library. Compared to wild-type STAT3, STAT3 beta lacks an internal domain of 50 base pairs located near the C terminus, This splice product is a naturally occurring isoform of STAT3 and encodes a 80-kDa protein. We found by reconstitution of the human IL-5R in COS cells that like STAT3, STAT3 beta is phosphorylated on tyrosine and binds to the pIRE from the ICAM-1 promoter after IL-5 stimulation. However, STAT3 beta fails to activate a pIRE containing promoter in transient transfection assays. Instead, co-expression of STAT3 beta inhibits the transactivation potential of STAT3. These results suggests that STAT3 beta functions as a negative regulator of transcription.