Rab7 prevents growth factor-independent survival by inhibiting cell-autonomous nutrient transporter expression
Rab7 prevents growth factor-independent survival by inhibiting cell-autonomous nutrient transporter expression
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DOI：
10.1016/s1534-5807(03)00291-0
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发表时间：
2003-10-01
影响因子：
11.8
通讯作者：
Thompson, CB
中科院分区：
文献类型：
--
作者：
Edinger, AL;Cinalli, RM;Thompson, CB
生长因子去除导致葡萄糖和氨基酸转运蛋白的内吞作用和降解。在这里，我们表明，这一过程是在小GTTRab 7的主动控制下。在生长因子的存在下，Rab 7抑制营养转运蛋白的表达没有影响。然而，在生长因子剥夺的细胞中，阻断Rab 7功能阻止了葡萄糖和氨基酸转运蛋白从细胞表面的清除。当Rab 7被抑制时，生长因子剥夺的细胞保持其线粒体膜电位，并显示出延长的、生长因子非依赖性的、营养依赖性的细胞存活。因此，Rab 7通过限制细胞自主营养摄取而作为促凋亡蛋白发挥作用。与此一致，显性负性Rab 7与E1 A协同促进p53（-/-）小鼠胚胎成纤维细胞（MEFs）的转化。这些结果表明，限制营养转运蛋白表达的蛋白质阻止细胞自主生长和存活。
Growth factor withdrawal results in the endocytosis and degradation of transporter proteins for glucose and amino acids. Here, we show that this process is under the active control of the small GTPase Rab7. In the presence of growth factor, Rab7 inhibition had no effect on nutrient transporter expression. In growth factor-deprived cells, however, blocking Rab7 function prevented the clearance of glucose and amino acid transporter proteins from the cell surface. When Rab7 was inhibited, growth factor deprived cells maintained their mitochondrial membrane potential and displayed prolonged, growth factor-independent, nutrient-dependent cell survival. Thus, Rab7 functions as a proapoptotic protein by limiting cell-autonomous nutrient uptake. Consistent with this, dominant-negative Rab7 cooperated with E1A to promote the transformation of p53(-/-) mouse embryonic fibroblasts (MEFs). These results suggest that proteins that limit nutrient transporter expression function to prevent cell-autonomous growth and survival.