The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Anatomy and Histoembryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Molecular, Cellular, and Developmental Biology Department, University of California, Santa Barbara, CA, 93106, USA.
Nat Commun. 2020 Nov 12;11(1):5726. doi: 10.1038/s41467-020-19068-2.
Apoptosis is an ancient and evolutionarily conserved cell suicide program. During apoptosis, executioner caspase enzyme activation has been considered a point of no return. However, emerging evidence suggests that some cells can survive caspase activation following exposure to apoptosis-inducing stresses, raising questions as to the physiological significance and underlying molecular mechanisms of this unexpected phenomenon. Here, we show that, following severe tissue injury, Drosophila wing disc cells that survive executioner caspase activation contribute to tissue regeneration. Through RNAi screening, we identify akt1 and a previously uncharacterized Drosophila gene CG8108, which is homologous to the human gene CIZ1, as essential for survival from the executioner caspase activation. We also show that cells expressing activated oncogenes experience apoptotic caspase activation, and that Akt1 and dCIZ1 are required for their survival and overgrowth. Thus, survival following executioner caspase activation is a normal tissue repair mechanism usurped to promote oncogene-driven overgrowth.
细胞凋亡是一种古老而保守的细胞自杀程序。在细胞凋亡过程中，执行 caspase 酶的激活被认为是一个不可逆转的点。然而，新出现的证据表明，一些细胞在暴露于诱导凋亡的应激后可以存活下来，这引发了对这种意外现象的生理意义和潜在分子机制的质疑。在这里，我们表明，在严重的组织损伤后，存活下来的果蝇翅盘细胞执行 caspase 激活有助于组织再生。通过 RNAi 筛选，我们鉴定出 akt1 和一个以前未被描述的果蝇基因 CG8108，它与人类基因 CIZ1 同源，是从执行 caspase 激活中存活所必需的。我们还表明，表达激活的癌基因的细胞经历凋亡 caspase 激活，并且 Akt1 和 dCIZ1 是它们存活和过度生长所必需的。因此，执行 caspase 激活后的存活是一种正常的组织修复机制，被篡夺来促进癌基因驱动的过度生长。
