...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >The Immunosuppressant Rapamycin Mimics a Starvation-Like Signal Distinct from Amino Acid and Glucose Deprivation
【24h】

The Immunosuppressant Rapamycin Mimics a Starvation-Like Signal Distinct from Amino Acid and Glucose Deprivation

机译：免疫抑制剂雷帕霉素模拟与氨基酸和葡萄糖剥夺不同的饥饿样信号

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

RAFT1/FRAP/mTOR is a key regulator of cell growth and division and the mammalian target of rapamycin, an immunosuppressive and anticancer drug. Rapamycin deprivation and nutrient deprivation have similar effects on the activity of S6 kinase 1 (S6K1) and 4E-BP1, two downstream effectors of RAFT1, but the relationship between nutrient- and rapamycin-sensitive pathways is unknown. Using transcriptional profiling, we show that, in human BJAB B-lymphoma cells and murine CTLL-2 T lymphocytes, rapamycin treatment affects the expression of many genes involved in nutrient and protein metabolism. The rapamycin-induced transcriptional profile is distinct from those induced by glucose, glutamine, or leucine deprivation but is most similar to that induced by amino acid deprivation. In particular, rapamycin treatment and amino acid deprivation up-regulate genes involved in nutrient catabolism and energy production and down-regulate genes participating in lipid and nucleotide synthesis and in protein synthesis, turnover, and folding. Surprisingly, however, rapamycin had effects opposite from those of amino acid starvation on the expression of a large group of genes involved in the synthesis, transport, and use of amino acids. Supported by measurements of nutrient use, the data suggest that RAFT1 is an energy and nutrient sensor and that rapamycin mimics a signal generated by the starvation of amino acids but that the signal is unlikely to be the absence of amino acids themselves. These observations underscore the importance of metabolism in controlling lymphocyte proliferation and offer a novel explanation for immunosuppression by rapamycin.
机译：RAFT1 / FRAP / mTOR是细胞生长和分裂的关键调节剂，是雷帕霉素的哺乳动物靶标，雷帕霉素是一种免疫抑制和抗癌药物。雷帕霉素的剥夺和营养物质的缺乏对RAFT1的两个下游效应物S6激酶1（S6K1）和4E-BP1的活性具有相似的影响，但营养素和雷帕霉素敏感途径之间的关系尚不清楚。使用转录谱，我们显示，在人BJAB B淋巴瘤细胞和鼠类CTLL-2 T淋巴细胞中，雷帕霉素治疗会影响许多参与营养和蛋白质代谢的基因的表达。雷帕霉素诱导的转录谱不同于葡萄糖，谷氨酰胺或亮氨酸剥夺诱导的转录谱，但与氨基酸剥夺诱导的转录谱最相似。特别地，雷帕霉素治疗和氨基酸剥夺上调涉及营养分解代谢和能量产生的基因，而下调参与脂质和核苷酸合成以及蛋白质合成，周转和折叠的基因。然而，令人惊奇的是，雷帕霉素对氨基酸的合成，转运和使用中涉及的大量基因的表达具有与氨基酸饥饿相反的作用。在营养物使用的测量结果的支持下，数据表明RAFT1是一种能量和营养物传感器，雷帕霉素模拟由氨基酸饥饿产生的信号，但该信号不太可能是氨基酸本身不存在。这些发现强调了代谢在控制淋巴细胞增殖中的重要性，并为雷帕霉素的免疫抑制提供了新的解释。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号