| First Author | Park H | Year | 2012 |
| Journal | Immunity | Volume | 36 |
| Issue | 5 | Pages | 769-81 |
| PubMed ID | 22608497 | Mgi Jnum | J:187318 |
| Mgi Id | MGI:5436190 | Doi | 10.1016/j.immuni.2012.02.019 |
| Citation | Park H, et al. (2012) Disruption of Fnip1 reveals a metabolic checkpoint controlling B lymphocyte development. Immunity 36(5):769-81 |
| abstractText | The coordination of nutrient and energy availability with cell growth and division is essential for proper immune cell development and function. By using a chemical mutagenesis strategy in mice, we identified a pedigree that has a complete block in B cell development at the pre-B cell stage resulting from a deletion in the Fnip1 gene. Enforced expression of an immunoglobulin transgene failed to rescue B cell development. Whereas essential pre-B cell signaling molecules were activated normally in Fnip1-null pre-B cells, the metabolic regulators AMPK and mTOR were dysregulated, resulting in excessive cell growth and enhanced sensitivity to apoptosis in response to metabolic stress (pre-B cell receptor crosslinking, oncogene activation). These results indicate that Folliculin-interacting protein 1 (Fnip1) is vital for B cell development and metabolic homeostasis and reveal a metabolic checkpoint that may ensure that pre-B cells have sufficient metabolic capacity to support division, while limiting lymphomagenesis caused by deregulated growth. |
