NSP6调节过载诱导的自细胞死亡,并由KLHL22介导的全方位化调节
Xingyu Tao1, Yanan Wang1, Jiangbo Jin2
1Jiangxi Institute of Respiratory Disease, The Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang City 330006 Jiangxi, China; Jiangxi Clinical Research Center for Respiratory Diseases, Nanchang City 330006 Jiangxi, China; China-Japan Friendship Jiangxi Hospital, National Regional Center for Respiratory Medicine, Nanchang City 330200 Jiangxi, China.
严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 非结构性蛋白6 (NSP6) 通过引起过载和自会触发细胞死亡. 凯尔奇样蛋白22 (KLHL22) 降解NSP6,为2019年冠状病毒疾病 (COVID-19) 提供潜在的治疗点.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 非结构蛋白 (NSP) 对病毒复制至关重要,但它们的命运和病原发生中的作用尚不清楚.
- 了解NSP6的功能对于开发有效的COVID-19治疗至关重要.
研究的目的:
- 为了确定宿主细胞内的SARS-CoV-2 NSP6的命运.
- 研究NSP6在病毒病原发生中的作用及其作为治疗点的潜力.
主要方法:
- 研究NSP6对细胞死亡及其潜在机制的影响.
- 在人类细胞中检查了NSP6降解途径.
- 在患者PBMC中,与COVID-19严重程度相关的NSP6表达.
主要成果:
- 通过与EI24相互作用,NSP6诱导细胞死亡,增加细胞内 (Ca2+),并通过ULK1/RB1CC1和BECN1/PIK3C3通路激活自.
- NSP6蛋白质的稳定性由K48相关的无化调节,其中KLHL22被确定为负责其降解的E3结合酶.
- NSP6表达与SARS-CoV-2疾病严重程度有积极的相关性.
结论:
- 通过KLHL22介导的全方位化控制NSP6的稳定性,防止由过载引起的自细胞死亡.
- NSP6的细胞毒性作用及其与COVID-19严重程度的联系表明,向信号或NSP6降解作为治疗策略.
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