The ubiquitin ligase SCFFBXW7α promotes GATA3 degradation
Copyright policy )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.
- Stomatology Hospital China (People's Republic of)
- Peking University China (People's Republic of)
- Peking University Cancer Hospital China (People's Republic of)
- Tianjin Medical University China (People's Republic of)
- Peking University China (People's Republic of)
F-Box-WD Repeat-Containing Protein 7, SKP Cullin F-Box Protein Ligases, Time Factors, Cell Survival, Ubiquitination, Breast Neoplasms, GATA3 Transcription Factor, Cullin Proteins, Transfection, Glycogen Synthase Kinase 3, Proteolysis, MCF-7 Cells, Humans, Female, RNA Interference, Phosphorylation, Protein Binding, Signal Transduction
F-Box-WD Repeat-Containing Protein 7, SKP Cullin F-Box Protein Ligases, Time Factors, Cell Survival, Ubiquitination, Breast Neoplasms, GATA3 Transcription Factor, Cullin Proteins, Transfection, Glycogen Synthase Kinase 3, Proteolysis, MCF-7 Cells, Humans, Female, RNA Interference, Phosphorylation, Protein Binding, Signal Transduction
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