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Publication : Gfi1-mediated stabilization of GATA3 protein is required for Th2 cell differentiation.

First Author  Shinnakasu R Year  2008
Journal  J Biol Chem Volume  283
Issue  42 Pages  28216-25
PubMed ID  18701459 Mgi Jnum  J:142306
Mgi Id  MGI:3820831 Doi  10.1074/jbc.M804174200
Citation  Shinnakasu R, et al. (2008) Gfi1-mediated stabilization of GATA3 protein is required for Th2 cell differentiation. J Biol Chem 283(42):28216-25
abstractText  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.
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