Mind bomb-2 is an E3 ligase for notch ligand
Mind bomb-2 is an E3 ligase for notch ligand
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DOI：
10.1074/jbc.m501631200
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发表时间：
2005-06-10
影响因子：
4.8
通讯作者：
Kong, YY
中科院分区：
文献类型：
--
作者：
Koo, BK;Yoon, KJ;Kong, YY
斑马鱼基因，心灵炸弹(MIB)，编码一种蛋白质，积极调节Delta介导的Notch信号。它与Delta的胞内结构域相互作用，促进其泛素化和内吞作用。在寻找斑马鱼Mind Bomb的小鼠同源基因的过程中，我们在小鼠基因组中克隆了两个同源基因：一个是小鼠的同源基因(小鼠mib1)，另一个是命名为Mind Bomb-2的同源基因(Mind Bomb-2，MIB2)，它在进化上从果蝇到人类都是保守的。Mib1和MIB2在其C-末端环区都具有E3泛素连接酶活性，并通过其N-末端区域与非洲爪蛙Delta(XD)相互作用。MIB2还能够将泛素连接到XD，并将Delta的膜定位转移到细胞内的小泡上。重要的是，MIB2挽救了斑马鱼MIB(Ta52b)突变体中的神经元和血管缺陷。与Mib1和MIB2的功能相似之处在于，MIB2在成体组织中高表达，但在胚胎中几乎不表达，而mib1在胚胎和成体组织中都大量表达。这些数据表明，MIB2的功能与Mib1相似，但可能作为E3泛素连接酶在Notch信号转导中具有不同的作用。
The zebrafish gene, mind bomb (mib), encodes a protein that positively regulates of the Delta-mediated Notch signaling. It interacts with the intracellular domain of Delta to promote its ubiquitination and endocytosis. In our search for the mouse homologue of zebrafish mind bomb, we cloned two homologues in the mouse genome: a mouse orthologue (mouse mib1) and a paralogue, named mind bomb-2 (mib2), which is evolutionarily conserved from Drosophila to human. Both Mib1 and Mib2 have an E3 ubiquitin ligase activity in their C-terminal RING domain and interact with Xenopus Delta (XD) via their N-terminal region. Mib2 is also able to ligate ubiquitin to XD and shift the membrane localization of Delta to intracellular vesicles. Importantly, Mib2 rescues both the neuronal and vascular defects in the zebrafish mib(ta52b) mutants. In contrast to the functional similarities between Mib1 and Mib2, mib2 is highly expressed in adult tissues, but almost not at all in embryos, whereas mib1 is abundantly expressed in both embryos and adult tissues. These data suggest that Mib2 has functional similarities to Mib1, but might have distinct roles in Notch signaling as an E3 ubiquitin ligase.