Cul5-type Ubiquitin Ligase KLHDC1 Contributes to the Elimination of Truncated SELENOS Produced by Failed UGA/Sec Decoding
Cul5-type Ubiquitin Ligase KLHDC1 Contributes to the Elimination of Truncated SELENOS Produced by Failed UGA/Sec Decoding
复制标题
DOI：
10.1016/j.isci.2020.100970
复制
发表时间：
2020-03-27
期刊：
影响因子：
5.8
通讯作者：
Kamura, Takumi
中科院分区：
文献类型：
--
作者：
Okumura, Fumihiko;Fujiki, Yuha;Kamura, Takumi
UGA密码子信号蛋白质翻译终止，但它也可以翻译成硒代半胱氨酸（Sec，U），以产生含硒代半胱氨酸的蛋白质（硒蛋白）通过专用的机器。由于Sec掺入可能失败，含有Sec的较长蛋白质和缺乏Sec的较短蛋白质共存。Cul2型泛素连接酶最近被证明是不稳定的，这样的截短的蛋白质，然而，泛素连接酶的目标截短的蛋白质降解仍然不清楚。我们报告，Cul5型泛素连接酶KLHDC1的目标截短的SELENOS，硒蛋白，蛋白酶体降解。SELENOS参与内质网（ER）相关的降解，这与活性氧（ROS）的产生有关，U2OS细胞中KLHDC1的敲低降低了ER应激诱导的细胞死亡。敲除SELENOS增加了具有较低ROS水平的细胞群。我们的研究结果表明，除了Cul2型泛素连接酶，KLHDC1还参与消除截短的氧化还原酶失活的SELENOS，这对维持ROS水平和预防癌症发展至关重要。
The UGA codon signals protein translation termination, but it can also be translated into selenocysteine (Sec, U) to produce selenocysteine-containing proteins (selenoproteins) by dedicated machinery. As Sec incorporation can fail, Sec-containing longer and Sec-lacking shorter proteins co-exist. Cul2-type ubiquitin ligases were recently shown to destabilize such truncated proteins; however, which ubiquitin ligase targets truncated proteins for degradation remained unclear. We report that the Cul5-type ubiquitin ligase KLHDC1 targets truncated SELENOS, a selenoprotein, for proteasomal degradation. SELENOS is involved in endoplasmic reticulum (ER)-associated degradation, which is linked to reactive oxygen species (ROS) production, and the knockdown of KLHDC1 in U2OS cells decreased ER stress-induced cell death. Knockdown of SELENOS increased the cell population with lower ROS levels. Our findings reveal that, in addition to Cul2-type ubiquitin ligases, KLHDC1 is involved in the elimination of truncated oxidoreductase-inactive SELENOS, which would be crucial for maintaining ROS levels and preventing cancer development.