Three modules of zebrafish Mind bomb work cooperatively to promote Delta ubiquitination and endocytosis
Three modules of zebrafish Mind bomb work cooperatively to promote Delta ubiquitination and endocytosis
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DOI：
10.1016/j.ydbio.2003.11.010
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发表时间：
2004-03-15
影响因子：
2.7
通讯作者：
Corliss, DC
中科院分区：
文献类型：
--
作者：
Chen, WB;Corliss, DC
Notch信号传导活性的精确调节对于许多不同组织的发育至关重要。在这里，我们表明，斑马鱼插入突变Hi904减弱Notch信号，是等位基因的头脑炸弹。我们表明，思维炸弹蛋白显示E3泛素连接酶活性在体外，它与德尔塔和增强其泛素化和内化在转染细胞。此外，通过对Mind bomb的三个保守区域的功能分析，我们发现N端的一半是Delta缔合所需的，锚蛋白重复序列对Delta内化很重要，而环指是Delta泛素化所需的。因此，思维炸弹的三个功能不同的模块协同工作，通过关联、泛素化和内化Delta来调节Notch信号。(C)2004爱思唯尔公司All rights reserved.
Precise regulation of Notch signaling activity is critical for development of many different tissues. Here, we show that the zebrafish insertional mutation Hi904 attenuates Notch signaling, and is allelic to mind bomb. We show that Mind bomb protein displays E3 ubiquitin ligase activity in vitro and that it is associated with Delta and enhances its ubiquitination and internalization in transfected cells. Furthermore, by functional analysis of three conserved regions of Mind bomb, we show that the N-terminal half is required for Delta association, the ankyrin repeats are important for Delta internalization, and the ring fingers are required for Delta ubiquitination. Thus, the three functionally distinct modules of Mind bomb work cooperatively to regulate Notch signaling by associating with, ubiquitinating, and internalizing Delta. (C) 2004 Elsevier Inc. All rights reserved.