The N-end rule pathway is mediated by a complex of the RING-type Ubr1 and HECT-type Ufd4 ubiquitin ligases.
The N-end rule pathway is mediated by a complex of the RING-type Ubr1 and HECT-type Ufd4 ubiquitin ligases.
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DOI：
10.1038/ncb2121
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发表时间：
2010-12
影响因子：
21.3
通讯作者：
Varshavsky, Alexander
中科院分区：
文献类型：
--
作者：
Hwang, Cheol-Sang;Shemorry, Anna;Auerbach, Daniel;Varshavsky, Alexander
N-末端规则途径的底物通过其去稳定的N-末端残基被Ubr 1 E3泛素连接酶识别。我们以前的工作表明，Ubr 1 E3和Ufd 4 E3共同靶向Mgt 1 DNA修复蛋白的内部降解决定子。Ufd 4是泛素融合降解（UFD）途径的E3，其识别N-末端泛素部分。在这里，我们报告说，环型Ubr 1 E3和HECT型Ufd 4 E3相互作用，在物理上和功能上。虽然Ubr 1可以识别和聚泛素化的N-末端规则基板在Ufd 4的情况下，Ubr 1-Ufd 4复合物是更进行性的，因为它产生一个更长的基板连接的聚泛素链。相反，Ubr 1可以作为Ubr 1-Ufd 4复合物的多聚泛素化增强组分，靶向UFD底物。我们还发现Ubr 1可以识别N-末端泛素部分。这些和相关的进展统一了两个蛋白水解系统，已分别研究了二十多年。
Substrates of the N-end rule pathway are recognized by the Ubr1 E3 ubiquitin ligase through their destabilizing N-terminal residues. Our previous work showed that the Ubr1 E3 and the Ufd4 E3 co-target an internal degron of the Mgt1 DNA repair protein. Ufd4 is an E3 of the ubiquitin-fusion degradation (UFD) pathway that recognizes an N-terminal ubiquitin moiety. Here we report that the RING-type Ubr1 E3 and the HECT-type Ufd4 E3 interact, both physically and functionally. Although Ubr1 can recognize and polyubiquitylate an N-end rule substrate in the absence of Ufd4, the Ubr1-Ufd4 complex is more processive in that it produces a longer substrate-linked polyubiquitin chain. Conversely, Ubr1 can function as a polyubiquitylation-enhancing component of the Ubr1-Ufd4 complex in its targeting of UFD substrates. We also found that Ubr1 can recognize the N-terminal ubiquitin moiety. These and related advances unify two proteolytic systems that have been studied separately over two decades.
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影响因子：
16.8
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.172527399
发表时间：
2002-10-29
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
56.9
作者：
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通讯作者：
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