Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Nat Immunol. 2008 Jun;9(6):613-22. doi: 10.1038/ni.1612. Epub 2008 May 11.

Foxo1 directly regulates the transcription of recombination-activating genes during B cell development.

Author information

  • 1Department of Molecular & Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA.

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.

PMID:
18469817
[PubMed - indexed for MEDLINE]
PMCID:
PMC2612116
Free PMC Article

Images from this publication.See all images (8)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Write to the Help Desk