Structure and function of the Mind bomb E3 ligase in the context of Notch signal transduction.

Structure and function of the Mind bomb E3 ligase in the context of Notch signal transduction.
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DOI:
10.1016/j.sbi.2016.05.012
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发表时间:
2016-12
影响因子:
6.8
通讯作者:
Blacklow, Stephen C.
Blacklow, Stephen C.
中科院分区:
生物学2区
文献类型:
--
作者:
Guo, Bingqian;McMillan, Brian J.;Blacklow, Stephen C.

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Notch信号通路在多种不同谱系中的细胞命运决定和组织稳态中具有关键作用。在正常Notch信号传导的情况下,“信号接收”细胞的Notch受体被来自相邻“信号发送”细胞的Notch配体反式激活。在几种模式生物中的遗传学研究已经确定,Notch配体的泛素化及其调节的内吞作用对于这种激活信号的传递是必不可少的。在哺乳动物中,这种泛素化步骤依赖于蛋白质Mind bomb 1(Mib 1),一种大型多结构域RING型E3连接酶及其与Notch配体分子的细胞内尾部的直接相互作用。在这里,我们讨论了我们目前的理解,思维炸弹的结构和机制的背景下,Notch信号和超越。
The Notch signaling pathway has a critical role in cell fate determination and tissue homeostasis in a variety of different lineages. In the context of normal Notch signaling, the Notch receptor of the “signal-receiving” cell is activated in trans by a Notch ligand from a neighboring “signal-sending” cell. Genetic studies in several model organisms have established that ubiquitination of the Notch ligand, and its regulated endocytosis, is essential for transmission of this activation signal. In mammals, this ubiquitination step is dependent on the protein Mind bomb 1 (Mib1), a large multi-domain RING-type E3 ligase, and its direct interaction with the intracellular tails of Notch ligand molecules. Here, we discuss our current understanding of Mind bomb structure and mechanism in the context of Notch signaling and beyond.
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