TIGAR, a p53-inducible regulator of glycolysis and apoptosis
TIGAR, a p53-inducible regulator of glycolysis and apoptosis
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DOI：
10.1016/j.cell.2006.05.036
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发表时间：
2006-07-14
期刊：
影响因子：
64.5
通讯作者：
Vousden, Karen H.
中科院分区：
文献类型：
--
作者：
Bensaad, Karim;Tsuruta, Atsushi;Vousden, Karen H.
p53肿瘤抑制蛋白通过多种机制阻止癌症的发展，包括诱导细胞周期阻滞、细胞凋亡和维持基因组稳定性。我们已经鉴定出p53诱导基因TIGAR （p53诱导糖酵解和凋亡调节因子）。TIGAR的表达降低了细胞中果糖-2,6-二磷酸水平，导致糖酵解抑制和细胞内活性氧（ROS）水平的整体降低。TIGAR的这些功能与保护细胞免受ros相关凋亡的能力相关，因此，内源性TIGAR表达的下调使细胞对p53诱导的死亡敏感。因此，TIGAR的表达可能调节对p53的凋亡反应，使细胞在面对可能被逆转或修复的轻度或短暂应激信号时存活。响应TIGAR的细胞内ROS水平的降低也可能在p53保护基因组损伤积累的能力中发挥作用。
The, p53 tumor-suppressor protein prevents cancer development through various mechanisms, including the induction of cell-cycle arrest, apoptosis, and the maintenance of genome stability. We have identified a p53-inducible gene named TIGAR (TP53-induced glycolysis and apoptosis regulator). TIGAR expression lowered fructose-2,6-bisphosphate levels in cells, resulting in an inhibition of glycolysis and an overall decrease in intracellular reactive oxygen species (ROS) levels. These functions of TIGAR correlated with an ability to protect cells from ROS-associated apoptosis, and consequently, knockdown of endogenous TIGAR expression sensitized cells to p53-induced death. Expression of TIGAR may therefore modulate the apoptotic response to p53, allowing survival in the face of mild or transient stress signals that may be reversed or repaired. The decrease of intracellular ROS levels in response to TIGAR may also play a role in the ability of p53 to protect from the accumulation of genomic damage.