A critical role of glucose-6-phosphate dehydrogenase in TAp73-mediated cell proliferation
A critical role of glucose-6-phosphate dehydrogenase in TAp73-mediated cell proliferation
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DOI：
10.4161/cc.27267
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发表时间：
2013-12-15
期刊：
影响因子：
4.3
通讯作者：
Yang, Xiaolu
中科院分区：
文献类型：
--
作者：
Jiang, Peng;Du, Wenjing;Yang, Xiaolu
戊糖磷酸途径（PPP）提供支持生物合成和抗氧化防御的核糖和NADPH。我们最近的研究结果表明，p53相关蛋白TAp73可以增强PPP通量。TAp73刺激PPP的限速酶葡萄糖-6-磷酸脱氢酶（G6PD）的表达。通过这种调节，TAp73促进大分子的积累，提高细胞抵抗氧化应激的能力。TAp73还调节其他代谢酶，这些靶标在TAp73介导的细胞生长中的相对重要性尚不清楚。本研究表明，与其他细胞系一样，TAp73在人肺癌H1299细胞中支持增殖和维持G6PD的表达是必需的。恢复G6PD的表达几乎完全恢复了TAp73敲低导致的细胞生长缺陷，提示G6PD是TAp73在这些细胞中的主要增殖靶点。G6PD在多种肿瘤中表达升高，与TAp73上调相关。这些结果表明，TAp73可能作为一种致癌基因，而G6PD可能是调控致癌生长的一个焦点。
The pentose phosphate pathway (PPP) provides ribose and NADPH that support biosynthesis and antioxidant defense. Our recent findings suggest that the p53-related protein TAp73 enhances the PPP flux. TAp73 stimulates the expression of glucose-6-phophate dehydrogenase (G6PD), the rate-limiting enzymes of the PPP. Through this regulation, TAp73 promotes the accumulation of macromolecules and increases cellular capability to withstand oxidative stresses. TAp73 also regulates other metabolic enzymes, and the relative importance of these targets in TAp73-mediated cell growth is not well understood. Here we show that, like in other cell lines, TAp73 is required for supporting proliferation and maintaining the expression of G6PD in the human lung cancer H1299 cells. Restoration of G6PD expression almost fully rescues the defects in cell growth caused by TAp73 knockdown, suggesting that G6PD is the major proliferative target of TAp73 in these cells. G6PD expression is elevated in various tumors, correlating with the upregulation of TAp73. These results indicate that TAp73 may function as an oncogene, and that G6PD is likely a focal point of regulation in oncogenic growth.