A novel RP2 missense mutation Q158P identified in an X-linked retinitis pigmentosa family impaired RP2 protein stability
A novel RP2 missense mutation Q158P identified in an X-linked retinitis pigmentosa family impaired RP2 protein stability
复制标题
在 X 连锁视网膜色素变性家族中发现的新型 RP2 错义突变 Q158P 损害了 RP2 蛋白稳定性
DOI：
10.1016/j.gene.2019.05.006
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发表时间：
2019
期刊：
影响因子：
3.5
通讯作者：
Cui Xiukun
中科院分区：
文献类型：
--
作者：
Zhang Jing;Gao Fen;Du Chunxiao;Wang Jungai;Pi Xiahui;Guo Wenya;Li Jing;Li Hui;Ma Yuanfang;Zhang Wanting;Mu Hongmei;Hu Yanzhong;Cui Xiukun
视网膜色素变性（RP）是最常见的遗传性视网膜变性疾病。X连锁RP占所有RP病例的近15%。在本研究中，我们在一个中国XLRP家系中发现了一个新的RP 2错义突变Q158 P。在ARPE-19细胞中，RP 2 Q158 P突变位于RP 2 TBCC结构域，并明显使RP 2蛋白不稳定。蛋白酶体抑制剂MG 132可使RP 2 Q158 P蛋白水平恢复。与此同时，低剂量的硼替佐米和卡非佐米（另两种已被批准用于多发性骨髓瘤临床治疗的蛋白酶体抑制剂）也可以挽救RP 2 Q158 P蛋白水平。与野生型RP 2蛋白相比，RP 2 Q158 P蛋白的泛素化程度明显增加。我们的发现拓宽了RP 2突变的范围，可能有助于更好地理解XLRP的分子机制。
Retinitis pigmentosa (RP) is the most common form of inherited retinal degenerative diseases. X-linked RP accounts for nearly 15% of all RP cases. In this study, we identified a novelRP2missense mutation Q158P in a Chinese XLRP family. TheRP2Q158P mutation located in the RP2 TBCC domain and obviously destabilized RP2 protein in ARPE-19 cells. The proteasome inhibitor MG132 could restore the RP2 Q158P protein levels. Meanwhile, lower doses of bortezomib and carfilzomib, another two proteasome inhibitors that have been approved in multiple myeloma clinical therapy, also could rescue the RP2 Q158P protein levels. The ubiquitination of RP2 Q158P protein obviously increased when compared with wild type RP2 protein. Our findings broadened the spectrum ofRP2mutations and may contribute a better understanding of the molecular mechanism of XLRP.