Deubiquitinase OTUD6A promotes proliferation of cancer cells via regulating Drp1 stability and mitochondrial fission.
Deubiquitinase OTUD6A promotes proliferation of cancer cells via regulating Drp1 stability and mitochondrial fission.
复制标题
去泛素酶 OTUD6A 通过调节 Drp1 稳定性和线粒体裂变促进癌细胞增殖
DOI：
10.1002/1878-0261.12825
复制
发表时间：
2020-12
影响因子：
6.6
通讯作者：
Long J
中科院分区：
文献类型：
--
作者：
Shi L;Liu J;Peng Y;Zhang J;Dai X;Zhang S;Wang Y;Liu J;Long J
OTUD 6A去泛素化并稳定Drp 1，从而促进线粒体形态和肿瘤发生的调节。OTUD6A的缺失导致较低的Drp1水平并抑制线粒体分裂，因此受影响的细胞不易发生肿瘤。相反，OTUD 6A的过表达增加了Drp1水平及其蛋白质半衰期，并增强了癌细胞生长。 动力蛋白相关蛋白1（Drp1）是一种负责线粒体分裂的胞质蛋白，在包括癌症在内的多种人类疾病的发生和发展中至关重要。然而，Drp1的调控，特别是其泛素化，仍然不清楚。在这项研究中，我们报告了卵巢肿瘤相关蛋白酶去泛素化酶6A（OTUD 6A）去泛素化和稳定Drp 1，从而促进线粒体形态和肿瘤发生的调节。OTUD 6A在患有结直肠癌的人类患者中上调。OTUD6A的消耗导致较低的Drp1水平和抑制的线粒体分裂，因此受影响的细胞不太容易发生肿瘤。相反，OTUD 6A的过表达增加了Drp1水平及其蛋白质半衰期，并增强了癌细胞生长。因此，我们的研究结果揭示了一种新的上游蛋白Drp1，其在肿瘤发生中的作用，部分是通过激活线粒体分裂介导的Drp1。
OTUD6A deubiquitylates and stabilizes Drp1, thereby facilitating regulation of mitochondrial morphology and tumorigenesis. The depletion of OTUD6A leads to lower Drp1 levels and suppresses mitochondrial fission, and the affected cells are consequently less prone to tumorigenesis. Conversely, the overexpression of OTUD6A increases Drp1 levels and its protein half‐life and enhances cancer cell growth. Dynamin‐related protein 1 (Drp1) is a cytosolic protein responsible for mitochondrial fission and is essential in the initiation and development of several human diseases, including cancer. However, the regulation of Drp1, especially of its ubiquitination, remains unclear. In this study, we report that the ovarian tumor‐associated protease deubiquitinase 6A (OTUD6A) deubiquitylates and stabilizes Drp1, thereby facilitating regulation of mitochondrial morphology and tumorigenesis. OTUD6A is upregulated in human patients with colorectal cancer. The depletion of OTUD6A leads to lower Drp1 levels and suppressed mitochondrial fission, and the affected cells are consequently less prone to tumorigenesis. Conversely, the overexpression of OTUD6A increases Drp1 levels and its protein half‐life and enhances cancer cell growth. Therefore, our results reveal a novel upstream protein of Drp1, and its role in tumorigenesis that is played, in part, through the activation of mitochondrial fission mediated by Drp1.
登录
查看更多内容
环型E3连接酶在结直肠癌中的功能意义和治疗意义。
影响因子：
8
作者：
Liu L;Wong CC;Gong B;Yu J
通讯作者：
Yu J
SIK2 通过 PI3K/AKT/HIF-1 α 通路和 Drp1 介导的卵巢癌线粒体裂变促进葡萄糖代谢重编程
影响因子：
9.7
作者：
Gao, Tian;Zhang, Xiaohong;Liu, Shujuan
通讯作者：
Liu, Shujuan
影响因子：
16
作者：
Gan W;Dai X;Lunardi A;Li Z;Inuzuka H;Liu P;Varmeh S;Zhang J;Cheng L;Sun Y;Asara JM;Beck AH;Huang J;Pandolfi PP;Wei W
通讯作者：
Wei W
影响因子：
3.7
作者：
Perga, Simona;Martire, Serena;Bertolotto, Antonio
通讯作者：
Bertolotto, Antonio
影响因子：
11.2
作者：
Gu, Li;Zhu, Yahui;Li, Youjun
通讯作者：
Li, Youjun