| First Author | Amin RH | Year | 2008 |
| Journal | Nat Immunol | Volume | 9 |
| Issue | 6 | Pages | 613-22 |
| PubMed ID | 18469817 | Mgi Jnum | J:136208 |
| Mgi Id | MGI:3795632 | Doi | 10.1038/ni.1612 |
| Citation | Amin RH, et al. (2008) Foxo1 directly regulates the transcription of recombination-activating genes during B cell development. Nat Immunol 9(6):613-22 |
| abstractText | 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. |
