Inhibition of ornithine decarboxylase induces STAT3 tyrosine phosphorylation and DNA binding in IEC-6 cells.
Inhibition of ornithine decarboxylase induces STAT3 tyrosine phosphorylation and DNA binding in IEC-6 cells.
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DOI：
10.1152/ajpcell.2000.278.2.c331
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发表时间：
2000-02
期刊：
影响因子：
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通讯作者：
L. Pfeffer;C. Yang;S. Pfeffer;A. Murti;S. McCormack;L. Johnson
中科院分区：
文献类型：
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作者：
L. Pfeffer;C. Yang;S. Pfeffer;A. Murti;S. McCormack;L. Johnson
多胺是大鼠肠粘膜IEC-6细胞系增殖所必需的。鸟氨酸脱羧酶（ODC）是催化多胺合成的第一步的酶。ODC抑制不仅导致多胺耗竭，还导致细胞增殖抑制，并调节即刻早期基因c-fos、c-myc和c-jun的表达，STAT转录因子家族成员与存在于启动子中的sis诱导元件（SIE）结合，调节多种重要基因的表达。在本研究中，我们测试的假设，即STAT 3转录因子，这是负责激活的急性期反应基因，被激活后抑制ODC。我们发现，抑制ODC快速诱导STAT 3激活，如通过STAT 3酪氨酸磷酸化、STAT 3从细胞质易位到细胞核以及STAT 3在SIE依赖性DNA-蛋白质复合物中的存在所确定的。抑制ODC后的STAT 3激活伴随着STAT 3依赖性报告构建体的激活。此外，长时间的多胺耗竭导致细胞STAT 3水平下调。
Polyamines are required for the proliferation of the rat intestinal mucosal IEC-6 cell line. Ornithine decarboxylase (ODC) is the enzyme that catalyzes the first step in polyamine synthesis. ODC inhibition not only leads to polyamine depletion but also leads to inhibition of cell proliferation and regulates the expression of the immediate-early genes c-fos, c-myc, and c-jun. Members of the signal transducers and activators of transcription (STAT) transcription factor family bind to the sis-inducible element (SIE) present in the promoters to regulate the expression of a variety of important genes. In the present study, we tested the hypothesis that the STAT3 transcription factor, which is responsible for activation of the acute phase response genes, is activated after inhibition of ODC. We found that inhibition of ODC rapidly induces STAT3 activation as determined by STAT3 tyrosine phosphorylation, translocation of STAT3 from the cytoplasm into the nucleus, and the presence of STAT3 in SIE-dependent DNA-protein complexes. STAT3 activation upon inhibition of ODC was accompanied by the activation of a STAT3-dependent reporter construct. Moreover, prolonged polyamine depletion resulted in downregulation of cellular STAT3 levels.