非催化性聚烯基基因的突变使TREX1不稳定,并放大cGAS-STING信号传输
Abraham Shim1, Xiaohan Luan2, Wen Zhou2
1Molecular Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
bioRxiv : the preprint server for biology
|January 23, 2024
概括
在催化领域之外的TREX1突变可能导致自身免疫性疾病. 一个特定的突变 (P61Q) 破坏了TREX1的稳定,损害了DNA清除,并激活了免疫反应.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 循环GMP-AMP合成酶 (cGAS) 刺激干扰素基因 (STING) 途径检测细胞质DNA,触发I型干扰素反应.
- 外核酶TREX1降解细胞质DNA,作为cGAS-STING通路的关键负调节器.
- 在TREX1的突变与自身炎症状况,如艾卡迪-古提耶氏综合征 (AGS) 和系统性红斑狼 (SLE) 相关.
结论:
- 在PPII基因中的TREX1突变,如P61Q,破坏了蛋白质的稳定.
- TREX1的不稳定会损害其外核酶功能,导致异常的cGAS-STING通路激活.
- 这些发现阐明了一种机制,即TREX1 PPII突变有助于自身免疫性疾病的发病.
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