Gfi1-mediated Stabilization of GATA3 Protein Is Required for Th2 Cell Differentiation
Copyright policy )Gfi1-mediated Stabilization of GATA3 Protein Is Required for Th2 Cell Differentiation
The differentiation of naive CD4 T cells into Th2 cells requires the T cell receptor-mediated activation of the ERK MAPK cascade. Little is known, however, in regard to how the ERK MAPK cascade regulates Th2 cell differentiation. We herein identified Gfi1 (growth factor independent-1) as a downstream target of the ERK MAPK cascade for Th2 cell differentiation. In the absence of Gfi1, interleukin-5 production and the change of histone modification at the interleukin-5 gene locus were severely impaired. Furthermore, the interferon gamma gene showed a striking activation in the Gfi1(-/-) Th2 cells. An enhanced ubiquitin/proteasome-dependent degradation of GATA3 protein was observed in Gfi1(-/-) Th2 cells, and the overexpression of GATA3 eliminated the defect of Th2 cell function in Gfi1-deficient Th2 cells. These data suggest that the T cell receptor-mediated induction of Gfi1 controls Th2 cell differentiation through the regulation of GATA3 protein stability.
- Chiba University Japan
Mice, Inbred BALB C, Proteasome Endopeptidase Complex, MAP Kinase Signaling System, Ubiquitin, Cell Differentiation, GATA3 Transcription Factor, Models, Biological, DNA-Binding Proteins, Mice, Inbred C57BL, Mice, Th2 Cells, Gene Expression Regulation, Animals, Humans, Interleukin-5, Transcription Factors
Mice, Inbred BALB C, Proteasome Endopeptidase Complex, MAP Kinase Signaling System, Ubiquitin, Cell Differentiation, GATA3 Transcription Factor, Models, Biological, DNA-Binding Proteins, Mice, Inbred C57BL, Mice, Th2 Cells, Gene Expression Regulation, Animals, Humans, Interleukin-5, Transcription Factors
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