The ubiquitin ligase SCFFBXW7α promotes GATA3 degradation.
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.
['Song|Nan|N|', 'Cao|Cheng|C|', 'Tang|Yiman|Y|', 'Bi|Liyuan|L|', 'Jiang|Yong|Y|', 'Zhou|Yongsheng|Y|', 'Song|Xin|X|', 'Liu|Ling|L|', 'Ge|Wenshu|W|']
D001943:Breast Neoplasms D002470:Cell Survival D044842:Cullin Proteins D000073979:F-Box-WD Repeat-Containing Protein 7 D005260:Female D050990:GATA3 Transcription Factor D038362:Glycogen Synthase Kinase 3 D006801:Humans D061986:MCF-7 Cells D010766:Phosphorylation D011485:Protein Binding D059748:Proteolysis D034622:RNA Interference D044843:SKP Cullin F-Box Protein Ligases D015398:Signal Transduction D013997:Time Factors D014162:Transfection D054875:Ubiquitination
ubiquitination E3 ligase breast cancer protein stability