STAT5-dependent cyclin D1 and bcl-xL expression in Bcr-Abl-transformed cells
STAT5-dependent cyclin D1 and bcl-xL expression in Bcr-Abl-transformed cells
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DOI：
10.1006/mcbr.2000.0231
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发表时间：
2000-05-01
期刊：
影响因子：
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通讯作者：
Koenderman, Leo
中科院分区：
文献类型：
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作者：
de Groot, Rolf P.;Raaijmakers, Jan A. M.;Koenderman, Leo
信号转导和转录激活因子（STAT）是一个转录因子家族，最初被鉴定为精氨酸诱导的基因表达的介导因子。我们和其他人最近表明，STAT 5在Bcr-Abl癌基因的细胞转化中也起着重要作用。在这里，我们表明，抗凋亡的bcl-xL基因产物和细胞周期调节因子细胞周期蛋白D1的Bcr-Abl转化细胞中的STAT 5的目标。在CML细胞系K562和异位表达Bcr-Abl的BaF 3细胞中，细胞周期蛋白D1和bcl-x启动子都具有高度活性。这些启动子的活性可以通过共转染STAT 5的显性负性（DN）突变体来强烈抑制。此外，细胞周期蛋白D1和bcl-x启动子含有STAT结合位点，STAT 5在Bcr-Abl转化的细胞中组成型结合于该位点。这些结果表明STAT 5通过诱导cyclin D1和bcl-xL的表达来促进Bcr-Abl的转化。
Signal transducers and activators of transcription (STATs) are a family of transcription factors that were originally identified as mediators of cytokine-induced gene expression. We and others have recently shown that STAT5 also plays a major role in cellular transformation by the Bcr-Abl oncogene. Here we show that the antiapoptotic bcl-xL gene product and the cell cycle regulator cyclin D1 are targets of STAT5 in Bcr-Abl-transformed cells. In the CML cell line K562 and in BaF3 cells ectopically expressing Bcr-Abl, both the cyclin D1 and bcl-x promoters are highly active. The activity of these promoters can be strongly repressed by cotransfection of a dominant negative (DN) mutant of STAT5. Moreover, the cyclin D1 and bcl-x promoters contain STAT binding sites to which STAT5 constitutively binds in Bcr-Abl transformed cells. These results suggest that STAT5 contributes to transformation by Bcr-Abl by induction of cyclin D1 and bcl-xL expression.