Deubiquitinase OTUD6A promotes proliferation of cancer cells via regulating Drp1 stability and mitochondrial fission

被引：35

作者：

Shi, Le ^{[1
,2
]}

Liu, Jing ^{[1
,2
]}

Peng, Yunhua ^{[1
,2
]}

Zhang, Jinfang ^{[3
]}

Dai, Xiangpeng ^{[4
]}

Zhang, Shuangxi ^{[1
,2
]}

Wang, Yongyao ^{[1
,2
]}

Liu, Jiankang ^{[1
,2
]}

Long, Jiangang ^{[1
,2
]}

机构：

[1] Xi An Jiao Tong Univ, Ctr Mitochondrial Biol & Med, Sch Life Sci & Technol, Key Lab Biomed Informat Engn,Minist Educ, Xian, Peoples R China

[2] Xi An Jiao Tong Univ, Frontier Inst Sci & Technol, 28 Xianning West Rd, Xian 710049, Peoples R China

[3] Wuhan Univ, Frontier Sci Ctr Immunol & Metab, Med Res Inst, Wuhan, Peoples R China

[4] Jilin Univ, Hosp 1, Key Lab Organ Regenerat & Transplantat, Minist Educ, Changchun, Peoples R China

来源：

MOLECULAR ONCOLOGY | 2020年 / 14卷 / 12期

基金：

中国国家自然科学基金;

关键词：

cancer cell growth; deubiquitination; Drp1; mitochondrial fission; OTUD6A; E3; LIGASES; DYNAMICS; PROTEIN; MORPHOLOGY; INHIBITION; APOPTOSIS; CYCLE; LUNG;

D O I：

10.1002/1878-0261.12825

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：3169 / 3183

页数：15

共 48 条

[1] Dynamic regulation of mitochondrial fission through modification of the dynamin-related protein Drp1 [J].