Disruption of Fnip1 reveals a metabolic checkpoint controlling B lymphocyte development.
Disruption of Fnip1 reveals a metabolic checkpoint controlling B lymphocyte development.
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DOI：
10.1016/j.immuni.2012.02.019
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发表时间：
2012-05-25
期刊：
影响因子：
32.4
通讯作者：
Iritani BM
中科院分区：
文献类型：
--
作者：
Park H;Staehling K;Tsang M;Appleby MW;Brunkow ME;Margineantu D;Hockenbery DM;Habib T;Liggitt HD;Carlson G;Iritani BM
细胞生长和分裂过程中营养和能量的协调对免疫细胞的正常发育和功能至关重要。在小鼠中使用化学诱变策略，我们发现了一个由于Fnip1基因缺失而在前B细胞阶段完全阻断B细胞发育的家系。强制表达一种免疫球蛋白转基因不能挽救B细胞的发育。尽管在fnip1缺失的前b细胞中，必需的前b细胞信号分子被正常激活，但代谢调节因子AMPK和mTOR被失调，导致细胞过度生长和对凋亡的敏感性增强，以应对代谢应激（前b细胞受体交联，癌基因激活）。这些结果表明卵泡蛋白相互作用蛋白1 （Fnip1）对B细胞的发育和代谢稳态至关重要，并揭示了一个代谢检查点，它可能确保前B细胞有足够的代谢能力来支持分裂，同时限制由生长失调引起的淋巴瘤发生。
The coordination of nutrient and energy availability with cell growth and division is essential for proper immune cell development and function. 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 due to 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 cross-linking, 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 which may ensure that pre-B cells have sufficient metabolic capacity to support division, while limiting lymphomagenesis caused by deregulated growth.
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影响因子：
56.9
作者：
Allen, Christopher D. C.;Okada, Takaharu;Cyster, Jason G.
通讯作者：
Cyster, Jason G.
影响因子：
64.5
作者：
Narkar VA;Downes M;Yu RT;Embler E;Wang YX;Banayo E;Mihaylova MM;Nelson MC;Zou Y;Juguilon H;Kang H;Shaw RJ;Evans RM
通讯作者：
Evans RM
影响因子：
64.8
作者：
通讯作者：
--
MYC刺激B淋巴细胞分化并放大钙信号传导。
DOI：
10.1083/jcb.200704173
发表时间：
2007-11-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
Habib T;Park H;Tsang M;de Alborán IM;Nicks A;Wilson L;Knoepfler PS;Andrews S;Rawlings DJ;Eisenman RN;Iritani BM
通讯作者：
Iritani BM
DOI：
10.1158/1078-0432.ccr-09-0889
发表时间：
2009-11-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Dang CV;Le A;Gao P
通讯作者：
Gao P