期刊
IMMUNITY
卷 36, 期 5, 页码 769-781出版社
CELL PRESS
DOI: 10.1016/j.immuni.2012.02.019
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类别
资金
- University of Washington [4162]
- NIH [K26RR024462]
- MMPC [09MCG96]
- ITHS [UL1RR05014, P30 CA15704]
- Celltech RD, Inc.
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 preB 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.
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