Inhibition of proteasomal degradation by the Gly-Ala repeat of Epstein-Barr virus is influenced by the length of the repeat and the strength of the degradation signal
Inhibition of proteasomal degradation by the Gly-Ala repeat of Epstein-Barr virus is influenced by the length of the repeat and the strength of the degradation signal
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DOI：
10.1073/pnas.140217397
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发表时间：
2000-07-18
影响因子：
11.1
通讯作者：
Masucci, MG
中科院分区：
文献类型：
--
作者：
Dantuma, NP;Heessen, S;Masucci, MG
Epstein-Barr病毒核抗原-1的Gly-Ala重复序列（GAr）是抑制顺式泛素/蛋白酶体依赖性蛋白水解的可转移元件。我们已经研究了这种抑制活性，通过使用绿色荧光蛋白为基础的报告，已针对蛋白水解的N端规则或泛素融合降解信号，导致不同程度的不稳定。绿色荧光蛋白底物的降解被抑制插入的25-aa GAr，但强烈不稳定的记者只得到部分保护。保护作用可以通过增加重复序列的长度来增强。然而，含有Ub-R和泛素融合降解信号的报告基因即使在239-aa GAr存在下也被降解。因此，插入一个强大的降解信号解除了EB病毒核抗原-1蛋白酶体降解的阻断。我们的研究结果表明，天然底物的营业额可能是微调的GAR样序列，抵消蛋白酶体破坏的靶向信号。
The Gly-Ala repeat (GAr) of the Epstein-Barr virus nuclear antigen-1 is a transferable element that inhibits in cis ubiquitin/proteasome-dependent proteolysis. We have investigated this inhibitory activity by using green fluorescent protein-based reporters that have been targeted for proteolysis by N end rule or ubiquitin-fusion degradation signals, resulting in various degrees of destabilization. Degradation of the green fluorescent protein substrates was inhibited on insertion of a 25-aa GAr, but strongly destabilized reporters were protected only partially. Protection could be enhanced by increasing the length of the repeat. However, reporters containing the Ub-R and ubiquitin-fusion degradation signals were degraded even in the presence of a 239-aa GAr. In accordance, insertion of a powerful degradation signal relieved the blockade of proteasomal degradation in Epstein-Barr virus nuclear antigen-1. Our findings suggest that the turnover of natural substrates may be finely tuned by GAr-like sequences that counteract targeting signals for proteasomal destruction.