Regulation of the Drosophila transcription factor, Cubitus interruptus, by two conserved domains
Regulation of the Drosophila transcription factor, Cubitus interruptus, by two conserved domains
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DOI：
10.1016/j.ydbio.2005.12.020
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发表时间：
2006-03-15
影响因子：
2.7
通讯作者：
Holmgren, RA
中科院分区：
文献类型：
--
作者：
Croker, JA;Ziegenhorn, SL;Holmgren, RA
刺猬信号是包括果蝇在内的许多生物发育所必需的。在果蝇中，Hh通过调节转录因子Cubitus interruptus （Ci）来塑造胚胎表皮和幼虫的影像盘。迄今为止，已经确定了三个调控水平：蛋白水解加工成抑制因子，核进口和激活。在本报告中，我们描述了在脊椎动物同源物GLI1、GL12和GLI3中保守的两个Ci结构域的功能。一个结构域包括五个C-2-H-2锌指中的前两个。虽然在GLI/Ci家族的所有成员中都是保守的，但前两个手指似乎与DNA靶序列没有显著的接触。缺少该区域的Ci蛋白仍然能够与细胞质复合体相互作用并激活胚胎和翅膀成像盘的转录，但它不再被加工成阻遏物形式。第二个结构域称为NR，即“n端调控”，与融合抑制子结合。该区域的缺失对胚胎的形成影响不大，但损害了Ci的细胞质保留。分析该结构域的氨基酸序列，鉴定出11条完全保守的丝氨酸和1条酪氨酸。我们提出这个区域可能被修饰，可能是通过磷酸化，来调节Ci核的输入。(C) 2005爱思唯尔公司版权所有。
Hedgehog signaling is required for the development of many organisms, including Drosophila. In flies, Hh patterns the embryonic epidermis and larval imaginal discs by regulating the transcription factor, Cubitus interruptus (Ci). To date, three levels of regulation have been identified: proteolytic processing into a repressor, nuclear import, and activation. In this report, we characterize the function of two Ci domains that are conserved in the vertebrate homologues, GLI1, GL12, and GLI3. One domain includes the first two of five C-2-H-2 zinc-fingers. While conserved in all members of the GLI/Ci family, the first two fingers do not appear to make significant contacts with the DNA target sequence. Ci protein lacking this region is still able to interact with the cytoplasmic complex and activate transcription in embryos and wing imaginal discs, but it is no longer processed into the repressor form. The second domain, termed NR for "N-terminal Regulatory", binds Suppressor of Fused. Deletion of this region has little effect on embryonic patterning, but compromises cytoplasmic retention of Ci. Analysis of the amino acid sequence of this domain identifies 11 perfectly conserved serines and one tyrosine. We propose that this region may be modified, possibly by phosphorylation, to regulate Ci nuclear import. (C) 2005 Elsevier Inc. All rights reserved.