NDLI: Transcription factors Foxo3a and Foxo1 couple the E3 ligase Cbl-b to the induction of Foxp3 expression in induced regulatory T cells

Content Provider	PubMed Central
Author	Harada, Yohsuke Harada, Yasuyo Elly, Chris Ying, Ge Paik, Ji-hye Depinho, Ronald A. Liu, Yun-cai
Copyright Year	2010
Abstract	The transcription factor Foxp3 is essential for optimal regulatory T (T reg) cell development and function. Here, we show that CD4+ T cells from Cbl-b RING finger mutant knockin or Cbl-b–deficient mice show impaired TGF-β–induced Foxp3 expression. These T cells display augmented Foxo3a phosphorylation, but normal TGF-β signaling. Expression of Foxo3a rescues Foxp3 expression in Cbl-b–deficient T cells, and Foxo3a deficiency results in defective TGF-β–driven Foxp3 induction. A Foxo3a-binding motif is present in a proximal region of the Foxp3 promoter, and is required for Foxo3a association. Foxo1 exerts similar effects as Foxo3a on Foxp3 expression. This study reveals that Foxo factors promote transcription of the Foxp3 gene in induced T reg cells, and thus provides new mechanistic insight into Foxo-mediated T cell regulation.
Related Links	http://dx.doi.org/10.1084/jem.20100004
Ending Page	1391
Page Count	11
Starting Page	1381
File Format	PDF
ISSN	00221007
e-ISSN	15409538
Journal	The Journal of Experimental Medicine
Issue Number	7
Volume Number	207
Language	English
Publisher	The Rockefeller University Press
Publisher Date	2010-07-05
Access Restriction	Open
Rights Holder	The Rockefeller University Press
Subject Keyword	Immunology Immunology and Allergy Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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