卡塞普辛K的抑制会通过Syk/SHP2/Src/OTUB1轴介导的信号传输诱导猛龙破坏稳定和线粒体功能障碍
Seung Un Seo1, Seon Min Woo1, Taeg Kyu Kwon2,3
1Department of Immunology, School of Medicine, Keimyung University, Daegu, 42601, South Korea.
Cell death & disease
|June 17, 2023
概括
这项研究揭示了抑制甲素K如何影响癌症中的猛禽途径. 它确定了一个Syk/SHP2/Src/OTUB1信号轴,这可能是癌症管理的治疗目标.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 猛龙信号通路对于癌症的进展至关重要.
- 通过Src介导的OTUB1-Y26的化稳定了Raptor.
- 素K抑制 (odanacatib;ODN) 破坏了Raptor的稳定性,但机制尚不清楚.
研究的目的:
- 为了阐明催素K抑制诱导的OTUB1-Y26酸化和猛禽稳定的机制.
- 调查SHP2和Syk在这个途径中的作用.
- 为了探索对线粒体功能的影响.
主要方法:
- 利用了SHP2删除和药理抑制.
- 研究了腺氨酸激酶 (Syk) 酸化.
- 评估了线粒体反应性氧物种 (ROS),融合和功能障碍.
主要成果:
- 素K的抑制激活了SHP2,去化了OTUB1并破坏了Raptor的稳定.
- 删除SHP2增加了OTUB1-Y26酸化和猛禽表达.
- 素K抑制激活Syk,导致SHP2介导的OTUB1-Y26脱化和线粒体功能障碍.
结论:
- 赛克是一种上游激酶激活SHP2,调节ODN诱导的猛禽下调和线粒体功能障碍.
- 在癌症中,Syk/SHP2/Src/OTUB1信号轴是潜在的治疗标.
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