Cullin-3 regulates pattern formation, external sensory organ development and cell survival during Drosophila development
Cullin-3 regulates pattern formation, external sensory organ development and cell survival during Drosophila development
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DOI：
10.1016/j.mod.2004.07.007
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发表时间：
2004-12-01
影响因子：
2.6
通讯作者：
Skeath, JB
中科院分区：
文献类型：
--
作者：
Mistry, H;Wilson, BA;Skeath, JB
泛素介导的蛋白水解调节蛋白质的稳态丰度，并通过突然消除关键效应蛋白来控制细胞内稳态。多酶系统通过多泛素链的共价连接靶向蛋白质进行破坏。蛋白质泛素化的特异性和时间由泛素连接酶控制，如Skp 1-Cullin-F盒蛋白复合物。Cullin是SCF复合物的主要成分，并且已经涉及关键调节分子包括细胞周期蛋白E、β-连环蛋白和中断肘的降解。在这里，我们描述了果蝇Cullin-3同源基因的遗传鉴定和分子特征。Cullin-3功能的扰动在发育过程中具有多效性效应，包括外部感觉器官发育、图案形成以及细胞生长和存活的缺陷。Cullin-3的缺失或过表达分别导致外部感觉器官形成的增加或减少，这暗示Cullin-3在调节细胞向神经命运的定向中的功能。我们还发现Cullin-3功能通过调节全长Cubitus interruptus的稳定性来调节Hedgehog信号传导（0155）。Cullin-3功能在眼盘而非其他成虫盘中的丧失促进Ci 155的细胞自主积累。相反，Cullin-3的过表达导致C1155在翅、笼头和腿中的细胞自主稳定化，但不是眼、成虫盘，表明Cullin-3功能的组织特异性调节。Cullin-3表型的多样性突出了果蝇发育过程中靶向蛋白水解的重要性。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
Ubiquitin-mediated proteolysis regulates the steady-state abundance of proteins and controls cellular homoeostasis by abrupt elimination of key effector proteins. A multienzyme system targets proteins for destruction through the covalent attachment of a multiubiquitin chain. The specificity and timing of protein ubiquitination is controlled by ubiquitin ligases, such as the Skp1-Cullin-F box protein complex. Cullins are major components of SCF complexes, and have been implicated in degradation of key regulatory molecules including Cyclin E, beta-catenin and Cubitus interruptus. Here, we describe the genetic identification and molecular characterisation of the Drosophila Cullin-3 homologue. Perturbation of Cullin-3 function has pleiotropic effects during development, including defects in external sensory organ development, pattern formation and cell growth and survival. Loss or overexpression of Cullin-3 causes an increase or decrease, respectively, in external sensory organ formation, implicating Cullin-3 function in regulating the commitment of cells to the neural fate. We also find that Cullin-3 function modulates Hedgehog signalling by regulating the stability of full-length Cubitus interruptus (0155). Loss of Cullin-3 function in eye discs but not other imaginal discs promotes cell-autonomous accumulation of Ci155. Conversely, overexpression of Cullin-3 results in a cell-autonomous stabilisation of Ci155 in wing, haltere and leg, but not eye, imaginal discs suggesting tissue-specific regulation of Cullin-3 function. The diverse nature of Cullin-3 phenotypes highlights the importance of targeted proteolysis during Drosophila development. (C) 2004 Elsevier Ireland Ltd. All rights reserved.