a Department. of Pharmacology , University of Colorado School of Medicine , Aurora CO , USA.
Autophagy. 2018;14(8):1467-1468. doi: 10.1080/15548627.2018.1475819. Epub 2018 Jul 21.
The molecular machinery linking macroautophagy (autophagy hereafter) to apoptosis is still being elucidated. A recent study found that the transcription factor FOXO3/FOXO3A (forkhead box O3), which regulates autophagy, is itself regulated by basal autophagy to determine apoptosis sensitivity. Autophagy inhibition confers cell sensitivity to anti-cancer agents, and this effect is explained by the ability of FOXO3 to transactivate the pro-apoptotic gene BBC3/PUMA. Here, we discuss the possibility that FOXO3 acts as a cell surveillance mechanism to correct autophagy perturbations (i.e., autophagy inhibition), and confers apoptosis sensitization if this autophagy imbalance is not rectified.
将自噬（以下简称自噬）与细胞凋亡联系起来的分子机制仍在研究之中。最近的一项研究发现，调节自噬的转录因子 FOXO3/FOXO3A（叉头框蛋白 O3）本身受到基础自噬的调控，以决定细胞凋亡的敏感性。自噬抑制可使细胞对抗癌药物敏感，FOXO3 转录激活促凋亡基因 BBC3/PUMA 解释了这一作用。在此，我们讨论了 FOXO3 作为一种细胞监控机制的可能性，以纠正自噬失调（即自噬抑制），并在这种自噬失衡得不到纠正的情况下赋予细胞凋亡敏感性。
