Contribution of Lysine 11-linked Ubiquitination to MIR2-mediated Major Histocompatibility Complex Class I Internalization
Contribution of Lysine 11-linked Ubiquitination to MIR2-mediated Major Histocompatibility Complex Class I Internalization
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DOI：
10.1074/jbc.m110.112763
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发表时间：
2010-11-12
影响因子：
4.8
通讯作者：
Ishido, Satoshi
中科院分区：
文献类型：
--
作者：
Goto, Eiji;Yamanaka, Yuko;Ishido, Satoshi
多泛素链是通过将泛素部分依次添加到目标分子上而产生的，这是由E3泛素连接酶催化的特定赖氨酸残基之间的反应。Lys（48）连接的多泛素链和Lys（63）连接的多泛素链分别是蛋白酶体依赖性降解和信号转导的诱导剂。最近出现的概念是，多泛素链介导的调节甚至更复杂，因为在体内已经发现了各种类型的非典型多泛素链。在这里，我们证明了一种新的复杂泛素链在体内作为主要组织相容性复合体I类（MHCI）膜蛋白的内化信号。通过四环素诱导表达系统和定量质谱分析，我们发现卡波西肉瘤相关疱疹病毒的病毒E3泛素连接酶MIR2产生的多泛素链是一个Lys（11）和Lys（63）混合连锁链。这种新的泛素链可以通过与epsin1（一种含有泛素相互作用基序的接头分子）的关联，作为MHC I的内化信号。
The polyubiquitin chain is generated by the sequential addition of ubiquitin moieties to target molecules, a reaction between specific lysine residues that is catalyzed by E3 ubiquitin ligase. The Lys(48)-linked and Lys(63)-linked polyubiquitin chains are well established inducers of proteasome-dependent degradation and signal transduction, respectively. The concept has recently emerged that polyubiquitin chain-mediated regulation is even more complex because various types of atypical polyubiquitin chains have been discovered in vivo. Here, we demonstrate that a novel complex ubiquitin chain functions as an internalization signal for major histocompatibility complex class I (MHCI) membrane proteins in vivo. Using a tetracycline-inducible expression system and quantitative mass spectrometry, we show that the polyubiquitin chain generated by the viral E3 ubiquitin ligase of Kaposi sarcoma-associated herpesvirus, MIR2, is a Lys(11) and Lys(63) mixed-linkage chain. This novel ubiquitin chain can function as an internalization signal for MHC I through its association with epsin1, an adaptor molecule containing ubiquitin-interacting motifs.