The subcellular localization and activity of Drosophila cubitus interruptus are regulated at multiple levels.
The subcellular localization and activity of Drosophila cubitus interruptus are regulated at multiple levels.
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发表时间：
1999-11
期刊：
影响因子：
4.6
通讯作者：
Q. T. Wang;R. Holmgren
中科院分区：
文献类型：
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作者：
Q. T. Wang;R. Holmgren
果蝇转录因子Cubitus interruptus(Ci)在胚胎表皮和幼虫成像盘的形成过程中介导Hedgehog(HH)信号转导。在没有HH信号的情况下，Ci被切割以产生能够转录抑制的截断的核形式。HH信号稳定并激活全长的Ci蛋白，导致下游靶基因的强烈激活，包括补丁和十足瘫痪。许多分子参与了Ci的调节。这些分子的突变导致了Ci蛋白水平、Ci蛋白降解程度和Ci靶基因表达的变化。本文研究了CI的亚细胞定位和活性的调节。我们首先描述了Ci中的二分核局域信号(NLS)。我们认为Ci的亚细胞分布受到两种相反的力量的影响，即NLS的作用和至少两个靶向Ci到细胞质的区域的作用。我们的数据进一步表明，PKA或Costal-2活性的丧失并不能完全模拟HH信号，这表明Ci蛋白分解和Ci激活是两个不同的事件，它们通过不同的途径进行调节。最后，我们提出存在三个水平的表观Ci活性，对应于沿AP轴的三个区域，具有不同的基因表达和不同水平的HH信号。
Cubitus interruptus (Ci), a Drosophila transcription factor, mediates Hedgehog (Hh) signaling during the patterning of embryonic epidermis and larval imaginal discs. In the absence of Hh signal, Ci is cleaved to generate a truncated nuclear form capable of transcriptional repression. Hh signaling stabilizes and activates the full-length Ci protein leading to strong activation of downstream target genes including patched and decapentaplegic. A number of molecules have been implicated in the regulation of Ci. Mutations in these molecules lead to changes in Ci protein level, the extent of Ci proteolysis and the expression of Ci target genes. This paper examines the regulation of Ci subcellular localization and activity. We first characterize a bipartite nuclear localization signal (NLS) within Ci. We propose that the subcellular distribution of Ci is affected by two opposing forces, the action of the NLS and that of at least two regions targeting Ci to the cytoplasm. Further our data show that loss of PKA or Costal-2 activity does not fully mimic Hh signaling, demonstrating that Ci proteolysis and Ci activation are two distinct events which are regulated through different paths. Finally, we propose that there are three levels of apparent Ci activity, corresponding to three zones along the AP axis with different sets of gene expression and different levels of Hh signaling.