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PMID: 18701459 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The Journal of biological chemistry ·Vol. 283 ·No. 42 ·2008-10-17 ·Pages 28216-25

Shinnakasu R, Yamashita M, Kuwahara M, Hosokawa H, Hasegawa A, Motohashi S, Nakayama T

Abstract

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.

MeSH Terms
Animals Cell Differentiation DNA-Binding Proteins/metabolism GATA3 Transcription Factor/metabolism Gene Expression Regulation Humans Interleukin-5/metabolism MAP Kinase Signaling System Mice Mice, Inbred BALB C Mice, Inbred C57BL Models, Biological Proteasome Endopeptidase Complex/metabolism Th2 Cells/metabolism Transcription Factors/metabolism Ubiquitin/chemistry
Chemicals
DNA-Binding Proteins GATA3 Transcription Factor Gata3 protein, mouse Gfi1 protein, mouse Interleukin-5 Transcription Factors Ubiquitin Proteasome Endopeptidase Complex
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Shinnakasu Ryo
Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba 260-8670, Japan.
Yamashita Masakatsu
Kuwahara Makoto
Hosokawa Hiroyuki
Hasegawa Akihiro
Motohashi Shinichiro
Nakayama Toshinori
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
DOI
10.1074/jbc.M804174200
Published
2008-10-17
Epub
2008-00-13
Pages
28216-25
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC2661392
Subset
IM
External Links
PubMed source DOI: 10.1074/jbc.M804174200 PMC Full Text View journal details
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