Re-thinking cell cycle regulators: the cross-talk with metabolism.
Re-thinking cell cycle regulators: the cross-talk with metabolism.
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DOI：
10.3389/fonc.2013.00004
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发表时间：
2013
影响因子：
4.7
通讯作者：
Fajas L
中科院分区：
文献类型：
--
作者：
Fajas L
对缺乏细胞周期调节因子（包括 E2F1、cdk4 和 pRB）的基因工程小鼠的分析表明，主要表型是代谢紊乱。这些关键的细胞周期调节剂有助于脂质合成、葡萄糖产生、胰岛素分泌和糖酵解代谢。研究表明，这些途径的失调会导致代谢紊乱和相关代谢疾病，例如肥胖和 II 型糖尿病。细胞周期蛋白-cdk-Rb-E2F1 通路除了在细胞周期调节和癌症中的作用外，还调节脂肪生成。还表明E2F1直接参与胰腺生长和功能的调节。同样，细胞周期蛋白 D3、cdk4 和 cdk9 也是对整个有机体代谢具有强烈影响的脂肪形成因子。这些例子支持了细胞周期调节蛋白也调节代谢过程的新兴观点。即使在非增殖细胞中，这些细胞周期调节剂也会被胰岛素和葡萄糖激活。最重要的是，这些细胞周期调节剂触发正常细胞和癌细胞增殖所需的适应性代谢转换。这些变化包括脂质合成增加、氧化代谢减少和糖酵解代谢增加。总之，这些因子是合成代谢生物合成过程的重要调节剂，同时阻断氧化和分解代谢途径，这让人想起癌细胞的代谢。
Analysis of genetically engineered mice deficient in cell cycle regulators, including E2F1, cdk4, and pRB, showed that the major phenotypes are metabolic perturbations. These key cell cycle regulators contribute to lipid synthesis, glucose production, insulin secretion, and glycolytic metabolism. It has been shown that deregulation of these pathways can lead to metabolic perturbations and related metabolic diseases, such as obesity and type II diabetes. The cyclin–cdk–Rb–E2F1 pathway regulates adipogenesis in addition to its well-described roles in cell cycle regulation and cancer. It was also shown that E2F1 directly participates in the regulation of pancreatic growth and function. Similarly, cyclin D3, cdk4, and cdk9 are also adipogenic factors with strong effects on whole organism metabolism. These examples support the emerging notion that cell cycle regulatory proteins also modulate metabolic processes. These cell cycle regulators are activated by insulin and glucose, even in non-proliferating cells. Most importantly, these cell cycle regulators trigger the adaptive metabolic switch that normal and cancer cells require in order to proliferate. These changes include increased lipid synthesis, decreased oxidative metabolism, and increased glycolytic metabolism. In summary, these factors are essential regulators of anabolic biosynthetic processes, blocking at the same time oxidative and catabolic pathways, which is reminiscent of cancer cell metabolism.