当前位置: X-MOL 学术Mol. Ther. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Dual role of deubiquitinating enzyme USP19 regulates mitotic progression and tumorigenesis by stabilizing survivin
Molecular Therapy ( IF 12.4 ) Pub Date : 2022-08-01 , DOI: 10.1016/j.ymthe.2022.07.019
Arun Pandian Chandrasekaran 1 , Apoorvi Tyagi 1 , Naresh Poondla 1 , Neha Sarodaya 1 , Janardhan Keshav Karapurkar 1 , Kamini Kaushal 1 , Chang-Hwan Park 2 , Seok-Ho Hong 3 , Kye-Seong Kim 2 , Suresh Ramakrishna 2
Affiliation  

Survivin is a component of the chromosomal passenger complex, which includes Aurora B, INCENP, and Borealin, and is required for chromosome segregation and cytokinesis. We performed a genome-wide screen of deubiquitinating enzymes for survivin. For the first time, we report that USP19 has a dual role in the modulation of mitosis and tumorigenesis by regulating survivin expression. Our results found that USP19 stabilizes and interacts with survivin in HCT116 cells. USP19 deubiquitinates survivin protein and extends its half-life. We also found that USP19 functions as a mitotic regulator by controlling the downstream signaling of survivin protein. Targeted genome knockout verified that USP19 depletion leads to several mitotic defects, including cytokinesis failure. In addition, USP19 depletion results in significant enrichment of apoptosis and reduces the growth of tumors in the mouse xenograft. We envision that simultaneous targeting of USP19 and survivin in oncologic drug development would increase therapeutic value and minimize redundancy.



中文翻译:

去泛素化酶 USP19 通过稳定生存素调节有丝分裂进程和肿瘤发生的双重作用

Survivin 是染色体乘客复合物的组成部分,该复合物包括 Aurora B、INCENP 和 Borealin,是染色体分离和胞质分裂所必需的。我们对生存素的去泛素化酶进行了全基因组筛选。我们首次报道 USP19 通过调节生存素表达在调节有丝分裂和肿瘤发生中发挥双重作用。我们的结果发现 USP19 在 HCT116 细胞中稳定并与存活蛋白相互作用。USP19 使生存素蛋白去泛素化并延长其半衰期。我们还发现 USP19 通过控制生存素蛋白的下游信号传导发挥有丝分裂调节剂的作用。靶向基因组敲除证实 USP19 缺失会导致多种有丝分裂缺陷,包括胞质分裂失败。此外,USP19 缺失导致细胞凋亡显着富集,并减少小鼠异种移植物中肿瘤的生长。我们预计,在肿瘤药物开发中同时靶向 USP19 和生存素将增加治疗价值并最大限度地减少冗余。

更新日期:2022-08-01
down
wechat
bug