The ubiquitin ligase SCFFBXW7α promotes GATA3 degradation

被引：8
|
作者：
Song, Nan [2 ]
Cao, Cheng [2 ]
Tang, Yiman [3 ]
Bi, Liyuan [4 ]
Jiang, Yong [1 ]
Zhou, Yongsheng [3 ]
Song, Xin [5 ]
Liu, Ling [2 ]
Ge, Wenshu [1 ]
机构：
[1] Peking Univ, Sch & Hosp Stomatol, Dept Gen Dent 2, 22 Zhongguancun South Ave, Beijing 100081, Peoples R China
[2] Tianjin Med Univ, Collaborat Innovat Ctr Tianjin Med Epigenet 2011, Tianjin Key Lab Med Epigenet, Dept Biochem & Mol Biol,Sch Basic Med Sci, Tianjin, Peoples R China
[3] Peking Univ, Sch & Hosp Stomatol, Dept Prosthodont, Beijing, Peoples R China
[4] Qingdao Haici Med Treatment Grp, Qingdao, Peoples R China
[5] Tianjin Med Univ, Res Ctr Basic Med Sci, Tianjin, Peoples R China
来源：
JOURNAL OF CELLULAR PHYSIOLOGY | 2018年 / 233卷 / 03期
基金：
中国国家自然科学基金;
关键词：
breast cancer; E3; ligase; protein stability; ubiquitination; LUMINAL CELL FATE; TUMOR-SUPPRESSOR; NERVOUS-SYSTEM; TRANSCRIPTION FACTORS; PROTEASOME SYSTEM; MAMMARY-GLAND; BREAST-CANCER; C-MYC; DIFFERENTIATION; FBW7;
D O I：
10.1002/jcp.26108
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
GATA3 is a key transcription factor in cell fate determination and its dysregulation has been implicated in various types of malignancies. However, how the abundance and function of GATA3 are regulated remains unclear. Here, we report that GATA3 is physically associated with FBXW7 alpha, and FBXW7 alpha destabilizes GATA3 through assembly of a SKP1-CUL1-F-box E3 ligase complex. Importantly, we showed that FBXW7 alpha promotes GATA3 ubiquitination and degradation in a GSK3 dependent manner. Furthermore, we demonstrated that FBXW7 alpha inhibits breast cancer cells survival through destabilizing GATA3, and the expression level of FBXW7 alpha is negatively correlated with that of GATA3 in breast cancer samples. This study indicated that FBXW7 alpha is a critical negative regulator of GATA3 and revealed a pathway for the maintenance of GATA3 abundance in breast cancer cells.
引用
收藏
页码：2366 / 2377
页数：12
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