Ubiquitination of E3 ubiquitin ligase TRIM5α and its potential role
Ubiquitination of E3 ubiquitin ligase TRIM5α and its potential role
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DOI：
10.1111/j.1742-4658.2008.06313.x
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发表时间：
2008-04-01
期刊：
影响因子：
5.4
通讯作者：
Kamitani, Tetsu
中科院分区：
文献类型：
--
作者：
Yamauchi, Keiko;Wada, Keiji;Kamitani, Tetsu
HIV-1有效地感染易感细胞并导致人类艾滋病。尽管艾滋病毒也可以进入旧大陆猴子的细胞，但它在逆转录之前会遇到阻碍。数据表明，这种物种特异性限制是由三部分基序（TRIM）5 α介导的，其分子功能尚未确定。在这里，我们表明，TRIM 5 α功能作为环指型E3泛素连接酶在体外和体内和泛素化本身与E2泛素结合酶UbcH 5 B。除了自身泛素化，我们还发现TRIM 5 α被另一种E3泛素连接酶Ro 52泛素化，并被YopJ去泛素化，YopJ是来自耶尔森氏菌的致病蛋白之一。因此，TRIM 5 α的泛素化由其自身和Ro 52催化，并由YopJ下调。出乎意料的是，尽管TRIM 5 α是泛素化的，但我们的结果显示蛋白酶体抑制剂MG 115和MG 132在HeLa细胞中不能稳定它，这表明TRIM 5 α的泛素化不会导致蛋白酶体降解。重要的是，TRIM 5 α明显与单个泛素分子缀合（单泛素化）。我们的monoubiquitin融合试验表明，monoubiquitination是TRIM 5 α从细胞质体易位到细胞质的信号。
HIV-1 efficiently infects susceptible cells and causes AIDS in humans. Although HIV can also enter the cells of Old World monkeys, it encounters a block before reverse transcription. Data have shown that this species-specific restriction is mediated by tripartite motif (TRIM)5 alpha, whose molecular function is still undefined. Here, we show that TRIM5 alpha functions as a RING-finger-type E3 ubiquitin ligase both in vitro and in vivo and ubiquitinates itself in cooperation with the E2 ubiquitin-conjugating enzyme UbcH5B. In addition to the self-ubiquitination, we show that TRIM5 alpha is ubiquitinated by another E3 ubiquitin ligase, Ro52, and deubiquitinated by YopJ, one of the pathogenic proteins derived from Yersinia species. Thus, the ubiquitination of TRIM5 alpha is catalyzed by itself and Ro52 and downregulated by YopJ. Unexpectedly, although TRIM5 alpha is ubiquitinated, our results have revealed that the proteasome inhibitors MG115 and MG132 do not stabilize it in HeLa cells, suggesting that the ubiquitination of TRIM5 alpha does not lead to proteasomal degradation. Importantly, TRIM5 alpha is clearly conjugated by a single ubiquitin molecule (monoubiquitination). Our monoubiquitin-fusion assay suggests that monoubiquitination is a signal for TRIM5 alpha to translocate from cytoplasmic bodies to the cytoplasm.