The Ubiquitin Ligase Scffbxw7 Alpha 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 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.