Regulation of Gli1 transcriptional activity in the nucleus by Dyrk1
Regulation of Gli1 transcriptional activity in the nucleus by Dyrk1
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DOI：
10.1074/jbc.m206743200
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发表时间：
2002-09-20
影响因子：
4.8
通讯作者：
Wu, DQ
中科院分区：
文献类型：
--
作者：
Mao, JH;Maye, P;Wu, DQ
为了研究双重特异性Yak 1相关激酶（Dyrk）1（一种核定位的双重特异性蛋白激酶）的细胞作用，我们使用报告基因测定法研究了其对转录调控的影响。我们发现Dyrk 1可以显著增强Gli 1依赖的基因转录，但不能增强LEF-1、c-Jun或Elk依赖的基因转录。在某种程度上，Dyrk 1通过将Gli 1保留在细胞核中来实现这一点。然而，我们也表明，Dyrk 1可以增强Gli 1-AHA，核输出突变体的转录活性，这表明Dyrk 1可能更直接地参与调节Gli 1的转录活性。此外，Dyrk 1与Sonic hedgehog（Shh）协同作用，诱导小鼠C3 H10 T1/2细胞的基因转录和分化。Shh刺激Dyrk 1激酶活性的失败表明，Dyrk 1可能不直接调节Shh信号通路，但功能上与它相互作用。因此，Gli 1的转录活性可能受到进一步的调节，在细胞核中的一个途径不同的Shh信号，一个由Dyrk 1介导的。
To investigate the cellular role of dual specificity Yak1-related kinase (Dyrk) 1, a nuclear localized dual specificity protein kinase, we examined its effect on transcriptional regulation using reporter gene assays. We found that Dyrk1 can substantially enhance Gli1-dependent, but not LEF-1-, c-Jun-, or Elk-dependent, gene transcription. In part, Dyrk1 does this through retaining Gli1 in the nucleus. However, we also demonstrate that Dyrk1 can enhance the transcriptional activity of Gli1-AHA, a nuclear export mutant, suggesting that Dyrk1 may be more directly involved in regulating the transcriptional activity of Gli1. In addition, Dyrk1 acted synergistically with Sonic hedgehog (Shh) to induce gene transcription and differentiation in mouse C3H10T1/2 cells. The failure of Shh to stimulate Dyrk1 kinase activity suggests that Dyrk1 may not be directly regulated by the Shh signaling pathway but functionally interacts with it. Thus, Gli1 transcriptional activity may be subjected to further regulation in the cell nucleus by a pathway distinct from Shh signaling, one mediated by Dyrk1.