Hedgehog stimulates maturation of Cubitus interruptus into a labile transcriptional activator
Hedgehog stimulates maturation of Cubitus interruptus into a labile transcriptional activator
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DOI：
10.1038/25533
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发表时间：
1998-12-31
期刊：
影响因子：
64.8
通讯作者：
Kalderon, D
中科院分区：
文献类型：
--
作者：
Ohlmeyer, JT;Kalderon, D
在果蝇中，蛋白质Hedgehog（Hh）的信号传导通过抑制全长Ci（Ci-155）蛋白水解成其缩短的Ci-75形式来改变转录因子Cubitus interruptus（Ci）的活性（1，2）。Ci-75主要存在于细胞核中，被认为是一种转录抑制因子（1），而有证据（3-5）表明Ci-155可能是一种转录激活因子（1，2，6）。然而，Ci-155仅在细胞质中检测到，在那里它与融合蛋白激酶（Fu）、融合抑制蛋白（Su（fu））和微管结合蛋白Costal-2相关（参考文献1、7 -9）。尚不清楚Ci-155如何成为核激活剂。我们在这里表明，苏（fu）的突变引起的Hh-靶基因的表达增加，以剂量依赖性的方式，同时降低Ci-155浓度的一些机制以外的蛋白水解为Ci-75，相反，消除Fu激酶活性降低Hh-靶基因的表达，而增加Ci-155浓度。我们提出，Fu激酶活性是Hh刺激Ci-155成熟为一个短暂的核转录激活因子所必需的，而Su（Fu）通过与Ci-155的化学计量相互作用反对这一成熟步骤。
In Drosophila, signalling by the protein Hedgehog (Hh) alters the activity of the transcription factor Cubitus interruptus (Ci) by inhibiting the proteolysis of full-length Ci (Ci-155) to its shortened Ci-75 form(1,2). Ci-75 is found largely in the nucleus and is thought to be a transcriptional repressor(1), whereas there is evidence(3-5) to indicate that Ci-155 may be a transcriptional activator(1,2,6). However, Ci-155 is detected only in the cytoplasm, where it is associated with the protein kinase Fused (Fu), with Suppressor of Fused (Su(fu)), and with the microtubule-binding protein Costal-2 (refs 1,7-9), It is not clear how Ci-155 might become a nuclear activator. We show here that mutations in Su(fu) cause an increase in the expression of Hh-target genes in a dose-dependent manner while simultaneously reducing Ci-155 concentration by some mechanism other than proteolysis to Ci-75, Conversely, eliminating Fu kinase activity reduces Hh-target gene expression while increasing Ci-155 concentration. We propose that Fu kinase activity is required for Hh to stimulate the maturation of Ci-155 into a short-lived nuclear transcriptional activator and that Su(fu) opposes this maturation step through a stoichiometric interaction with Ci-155.