Increased proteolytic processing of full-length Gli2 transcription factor reduces the hedgehog pathway activity in vivo.

Increased proteolytic processing of full-length Gli2 transcription factor reduces the hedgehog pathway activity in vivo.
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DOI:
10.1002/dvdy.22578
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发表时间:
2011-04
影响因子:
2.5
通讯作者:
Wang, Baolin
Wang, Baolin
中科院分区:
生物学3区
文献类型:
--
作者:
Li, Juan;Wang, Chengbing;Pan, Yong;Bai, Zengliang;Wang, Baolin

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Gli2和Gli3全长转录因子的蛋白水解加工成为阻遏物是Hedgehog(Hh)信号转导调控的关键步骤。Gli2和Gli3的差异加工受加工决定域(PDD)控制,但其意义尚不清楚。我们产生了Gli2突变等位基因Gli23PDD,其中Gli3PDD取代Gli2PDD。正如预期的那样,与Gli2相比,Gli23PDD被更有效地加工并且在不同的位置处加工,这表明PDD还决定了Gli2和Gli3在体内加工的程度和位点。Gli23 PDD突变体中Gli2阻遏物水平的增加降低了Hh途径活性。Gli23 PDD的加工仍然受Hh信号的调节。这些结果表明Gli2全长激活子和阻遏子之间的适当平衡对于Hh信号传导是必不可少的。
The proteolytic processing of Gli2 and Gli3 full-length transcription factors into repressors is a key step of the regulation in Hedgehog (Hh) signaling. The differential Gli2 and Gli3 processing is controlled by the processing determinant domain or PDD, but its significance is not clear. We generated a Gli2 mutant allele, Gli23PDD, in which the Gli3PDD substitutes for the Gli2PDD. As expected, Gli23PDD is processed more efficiently and at the different position as compared to Gli2, indicating that PDD also determines the extent and site of Gli2 and Gli3 processing in vivo. The increase in levels of the Gli2 repressor in Gli23PDD mutant reduces the Hh pathway activity. Gli23PDD processing is still regulated by Hh signaling. These results indicate that the proper balance between the Gli2 full-length activator and repressor is essential for Hh signaling.
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