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. |