The regulation of AMPK β1, TSC2, and PTEN expression by p53:: Stress, cell and tissue specificity, and the role of these gene products in modulating the IGF-1-AKT-mTOR pathways
The regulation of AMPK β1, TSC2, and PTEN expression by p53:: Stress, cell and tissue specificity, and the role of these gene products in modulating the IGF-1-AKT-mTOR pathways
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DOI：
10.1158/0008-5472.can-06-4149
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发表时间：
2007-04-01
期刊：
影响因子：
11.2
通讯作者：
Levine, Arnold J.
中科院分区：
文献类型：
--
作者：
Feng, Zhaohui;Hu, Wenwei;Levine, Arnold J.
胰岛素样生长因子1（IGF-1）-akt-MTOR途径感知营养和有丝分裂剂的可用性，并通过信号传导细胞生长和分裂来做出反应。 p53途径感知各种应力信号，这些信号将降低细胞生长和分裂的保真度，并通过引发细胞周期停滞，衰老或凋亡做出反应。这项研究探讨了XMPK的β1和β2亚基的四种p53调节的基因产物，这首先显示了p53蛋白，TSC2，PTEN，PTEN和IGF-BP3的调节，每个蛋白质对每个蛋白质进行负调节压力后的IGF-1-AKT-MTOR途径。这些基因产物在细胞类型和组织特异性的方式下显示在p53对照下表达，TSC2和PTEN蛋白在使用胰岛素依赖性能量代谢（骨骼肌肉，心脏，白色脂肪，肝，肝脏，肝，肝，肝，肝，肝，肝，肝，肝，肝，肝，肝，肝，肝，肝，肝，肝，肝，肝，肝，肝，肝，肝，肝，肝脏，肝，肝，肝，肝的和肾脏）。此外，这些基因以应力信号特异性方式受p53调节。 MTOR途径还与p53途径通信。小鼠胚胎成纤维细胞的葡萄糖饥饿后，AMPK磷酸化p53蛋白，但不会激活任何p53反应。在E1A转化的小鼠胚胎成纤维细胞的葡萄糖饥饿后，随后发生了p53介导的凋亡。因此，p53途径与IGF-1-AKT和MTOR途径之间存在很多通信。
The insulin-like growth factor 1 (IGF-1)-AKT-mTOR pathways sense the availability of nutrients and mitogens and respond by signaling for cell growth and division. The p53 pathway senses a variety of stress signals which will reduce the fidelity of cell growth and division, and responds by initiating cell cycle arrest, senescence, or apoptosis. This study explores four p53-regulated gene products, the beta 1 and beta 2 subunits of the XMPK, which are shown for the first time to be regulated by the p53 protein, TSC2, PTEN, and IGF-BP3, each of which negatively regulates the IGF-1-AKT-mTOR pathways after stress. These gene products are shown to be expressed under p53 control in a cell type and tissue-specific fashion with the TSC2 and PTEN proteins being coordinately regulated in those tissues that use insulin-dependent energy metabolism (skeletal muscle, heart, white fat, liver, and kidney). In addition, these genes are regulated by p53 in a stress signal-specific fashion. The mTOR pathway also communicates with the p53 pathway. After glucose starvation of mouse embryo fibroblasts, AMPK phosphorylates the p53 protein but does not activate any of the p53 responses. Upon glucose starvation of E1A-transformed mouse embryo fibroblasts, a p53-mediated apoptosis ensues. Thus, there is a great deal of communication between the p53 pathway and the IGF-1-AKT and mTOR pathways.