Article abstract
Nature Immunology 9, 613 - 622 (2008)
Published online: 11 May 2008 | doi:10.1038/ni.1612
Foxo1 directly regulates the transcription of recombination-activating genes during B cell development
Rupesh H Amin1 & Mark S Schlissel1
Abstract
Regulated expression of the recombinase RAG-1 and RAG-2 proteins is necessary for generating the vast repertoire of antigen receptors essential for adaptive immunity. Here, a retroviral cDNA library screen showed that the stress-regulated protein GADD45a activated transcription of the genes encoding RAG-1 and RAG-2 in transformed pro–B cells by a pathway requiring the transcription factor Foxo1. Foxo1 directly activated transcription of the Rag1-Rag2 locus throughout early B cell development, and a decrease in Foxo1 protein diminished the induction of Rag1 and Rag2 transcription in a model of receptor editing. We also found that transcription of Rag1 and Rag2 was repressed at the pro–B cell and immature B cell stages by the kinase Akt through its 'antagonism' of Foxo1 function. Thus, Foxo1 is a key regulator of Rag1 and Rag2 transcription in primary B cells.
- Department of Molecular & Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA.
Correspondence to: Mark S Schlissel1 e-mail: mss@berkeley.edu
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