Proliferation, but not growth, blocked by conditional deletion of 40S ribosomal protein S6

Proliferation, but not growth, blocked by conditional deletion of 40S ribosomal protein S6
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DOI:
10.1126/science.288.5473.2045
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发表时间:
2000-06-16
期刊:
影响因子:
56.9
通讯作者:
Thomas, G
Thomas, G
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Volarevic, S;Stewart, MJ;Thomas, G

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由于核糖体生物合成在细胞增殖中起着至关重要的作用,控制机制可能已经进化到识别这一关键合成代谢过程中的病变。为了测试这种可能性,我们有条件地删除了成年小鼠肝脏中编码40 S核糖体蛋白S6的基因。出乎意料的是,来自S6缺乏的禁食动物的肝脏对营养物的反应是生长的,即使40 S核糖体的生物合成被废除。然而,肝细胞不能增殖或诱导细胞周期蛋白E的表达后,部分肝切除术,尽管形成活性细胞周期蛋白D-CDK 4复合物。这些结果表明,废除40 S核糖体生物合成可能会诱导一个检查点控制,阻止细胞周期的进展。
Because ribosome biogenesis plays an essential role in cell proliferation, control mechanisms may have evolved to recognize Lesions in this critical anabolic process. To test this possibility, we conditionally deleted the gene encoding 40S ribosomal protein S6 in the Liver of adult mice. Unexpectedly, Livers from fasted animals deficient in S6 grew in response to nutrients even though biogenesis of 40S ribosomes was abolished. However, Liver cells failed to proliferate or induce cyclin E expression after partial hepatectomy, despite formation of active cyclin D-CDK4 complexes. These results imply that abrogation of 40S ribosome biogenesis may induce a checkpoint control that prevents cell cycle progression.