双化酶USP19通过稳定YAP促进肝细胞癌的进展
Zelin Tian1, Chen Xu1, Weixiang He2
1Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Medical University, Xi'an, China.
乌比基特异性酶19 (USP19) 稳定YAP蛋白,促进肝细胞癌 (HCC) 的生长和迁移. 在HCC组织中的USP19上调表明其作为这种癌症的治疗点的潜力.
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:
- 河马途径及其关键调节者,是-关联蛋白 (YAP),在肝细胞癌 (HCC) 的发展中至关重要.
- 导致HCC异常YAP激活的确切机制尚不完全理解.
研究的目的:
- 为了确定参与HCC中YAP调节的特定二化酶 (DUB),HCC.
- 阐明USP19在YAP稳定中的作用及其对HCC进展的影响.
主要方法:
- 对DUB siRNA库进行选,以识别与YAP交互的DUB.
- 在体外和体内实验中评估USP19在HCC细胞和组织中的功能.
- 对YAP无处可见位 (K76,K90) 和无处可见链链接 (K48,K11) 的分析.
主要成果:
- 乌比基特异性酶19 (USP19) 被确定为HCC.中YAP的特定DUB.
- USP19在K76和K90位点对YAP进行二基化,去除与K48和K11结合的基链,从而稳定YAP蛋白.
- 通过USP19 Knockdown降低了YAP表达及其向基因 (CTGF,CYR61,ANKRD1),抑制了HCC的扩散和迁移.
- USP19在HCC组织上升调节,与患者预后不佳相关.
结论:
- USP19通过duebiquitination稳定了YAP,促进了HCC的扩散和迁移.
- USP19代表了HCC中YAP的新型后翻译调节器.
- USP19是肝细胞癌治疗的潜在治疗标.
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