DNA damage regulates ARID1A stability via SCF ubiquitin ligase in gastric cancer cells

被引:0
|
作者
Jiang, Z. -H. [1 ]
Dong, X. -W. [2 ]
Shen, Y. -C. [1 ]
Qian, H. -L. [1 ]
Yan, M. [1 ]
Yu, Z. -H. [1 ]
He, H. -B. [1 ]
Lu, C. -D. [1 ]
Qiu, F. [1 ]
机构
[1] Li Huili Hosp, Ningbo Med Ctr, Dept Gastrointestinal Surg, Ningbo, Zhejiang, Peoples R China
[2] Li Huili Hosp, Ningbo Med Ctr, Dept Gastroenterol, Ningbo, Zhejiang, Peoples R China
关键词
ARID1A; SCF E3 ligase; Gastric cancer; Ubiquitination; MISMATCH REPAIR DEFICIENCY; EPSTEIN-BARR-VIRUS; MICROSATELLITE INSTABILITY; ENDOMETRIAL CARCINOMAS; EXPRESSION; MUTATIONS; ROLES;
D O I
暂无
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
OBJECTIVE: The gene product of the AT-rich interactive domain 1A (SWI-like) gene (ARID1A) is a member of the SWI/SNF adenosine triphosphate-dependent chromatin-remodeling complexes, which plays an essential role in controlling gene expression and is also involved in cancer development. ARID1A is frequently mutated in a wild variety of cancers and function as a tumor suppressor in several kinds of cancers. ARID1A was down-regulated in gastric cancer, and associated poor patient prognosis. However, how ARID1A protein is regulated in gastric cancer remains largely unknown. MATERIALS AND METHODS: Here, we show that ARID1A protein is rapidly ubiquitinated and degradated in gastric cancer cells in response to DNA damage treatment. RESULTS: Using genetic and pharmacologic Cullin inactivation coupled with in vitro ubiquitination assay, we demonstrate that ARID1A is a substrate of the Cullin-SKP1-F-box protein (SCF) complexes. Moreover, gastric cancer cells with forced expression of ARID1A showed an increased sensitivity to DNA damage reagents. Thus, our data uncovered a previous unknown posttranscriptional regulation of ARID1A by SCF E3 ligase in gastric cancer cells in DNA damage response. CONCLUSIONS: These findings suggest ARID1A might be a promising drug target in gastric cancer treatment.
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收藏
页码:3194 / 3200
页数:7
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