The ubiquitin ligase SCFFBXW7 alpha promotes GATA3 degradation
The ubiquitin ligase SCFFBXW7 alpha promotes GATA3 degradation
复制标题
泛素连接酶 SCFFBXW7 α 促进 GATA3 降解
DOI：
10.1002/jcp.26108
复制
发表时间：
2018
影响因子：
5.6
通讯作者：
Ge Wenshu
中科院分区：
文献类型：
--
作者：
Song Nan;Cao Cheng;Tang Yiman;Bi Liyuan;Jiang Yong;Zhou Yongsheng;Song Xin;Liu Ling;Ge Wenshu
GATA 3是决定细胞命运的关键转录因子，其失调与多种类型的恶性肿瘤有关。然而，GATA 3的丰度和功能如何调节仍不清楚。在这里，我们报告GATA 3与FBXW 7 α物理相关，FBXW 7 α通过组装SKP 1-CUL 1-F-box E3连接酶复合物使GATA 3不稳定。重要的是，我们发现FBXW 7 α以GSK 3依赖性方式促进GATA 3泛素化和降解。此外，我们证明了FBXW 7 α通过破坏GATA 3的稳定来抑制乳腺癌细胞的存活，并且在乳腺癌样品中FBXW 7 α的表达水平与GATA 3的表达水平呈负相关。这项研究表明，FBXW 7 α是GATA 3的关键负调节因子，并揭示了乳腺癌细胞中维持GATA 3丰度的途径。
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 FBXW7α, and FBXW7α destabilizes GATA3 through assembly of a SKP1‐CUL1‐F‐box E3 ligase complex. Importantly, we showed that FBXW7α promotes GATA3 ubiquitination and degradation in a GSK3 dependent manner. Furthermore, we demonstrated that FBXW7α inhibits breast cancer cells survival through destabilizing GATA3, and the expression level of FBXW7α is negatively correlated with that of GATA3 in breast cancer samples. This study indicated that FBXW7α is a critical negative regulator of GATA3 and revealed a pathway for the maintenance of GATA3 abundance in breast cancer cells.