Degradation of the Id2 developmental regulator: targeting via N-terminal ubiquitination
Degradation of the Id2 developmental regulator: targeting via N-terminal ubiquitination
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DOI：
10.1016/j.bbrc.2003.12.116
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发表时间：
2004-02-06
影响因子：
3.1
通讯作者：
Ciechanover, A
中科院分区：
文献类型：
--
作者：
Fajerman, I;Schwartz, AL;Ciechanover, A
通过泛素蛋白酶体系统（UPS）降解细胞蛋白包括：(i)产生底物锚定的多泛素降解信号；（ii） 26S蛋白酶体破坏标记蛋白，释放自由和可重复使用的泛素。对于大多数底物，认为第一个泛素片段与内部赖氨酸残基的epsilon-NH2基团共轭。最近的研究结果表明，对于一些蛋白质，第一个泛素片段以线性方式融合到蛋白质的游离α - nh2基团上。在这里，我们证明了分化抑制剂（或DNA结合抑制剂）2,Id2，在未分化和自我更新的细胞中下调基因表达，在其n端残基泛素化后被UPS降解。赖氨酸少（LL） Id2在泛素化后被蛋白酶体有效降解。Myc标签与Id2的n端而不是c端残基融合可以稳定蛋白质。此外，Id2的前15个n端残基的缺失稳定了该蛋白，这表明该结构域可能是泛素连接酶E3的识别元件。控制Id2稳定性的机制和结构动机可能对正常分化和恶性转化过程中蛋白质的调节具有重要意义。(C) 2003 Elsevier Inc.版权所有。
Degradation of cellular proteins via the ubiquitin proteasome system (UPS) involves: (i) generation of a substrate-anchored polyubiquitin degradation signal and (ii) destruction of the tagged protein by the 26S proteasome with release of free and reusable ubiquitin. For most substrates, it is believed that the first ubiquitin moiety is conjugated to a epsilon-NH2 group of an internal Lys residue. Recent findings indicate that for several proteins, the first ubiquitin moiety is fused, in a linear manner, to the free alpha-NH2 group of the protein. Here, we demonstrate that the inhibitor of differentiation (or inhibitor of DNA binding) 2, Id2, that downregulates gene expression in undifferentiated and self-renewing cells, is degraded by the UPS following ubiquitination at its N-terminal residue. Lysine-less (LL) Id2 is degraded efficiently by the proteasome following ubiquitination. Fusion of a Myc tag to the N-terminal but not to the C-terminal residue of Id2 stabilizes the protein. Furthermore, deletion of the first 15 N-terminal residues of Id2 stabilizes the protein, suggesting that this domain serves as a recognition element, possibly for the ubiquitin ligase, E3. The mechanisms and structural motives that govern Id2 stability may have important implications to the regulation of the protein during normal differentiation and malignant transformation. (C) 2003 Elsevier Inc. All rights reserved.