Akt1 and dCIZ1 promote cell survival from apoptotic caspase activation during regeneration and oncogenic overgrowth.
Akt1 and dCIZ1 promote cell survival from apoptotic caspase activation during regeneration and oncogenic overgrowth.
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DOI：
10.1038/s41467-020-19068-2
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发表时间：
2020-11-12
影响因子：
16.6
通讯作者：
Montell DJ
中科院分区：
文献类型：
--
作者：
Sun G;Ding XA;Argaw Y;Guo X;Montell DJ
细胞凋亡是一个古老的和进化保守的细胞自杀程序。在细胞凋亡过程中，执行者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，一些细胞可以生存的caspase激活后暴露于凋亡诱导的压力，提出了问题的生理意义和潜在的分子机制，这一意想不到的现象。在这里，我们表明，严重的组织损伤后，果蝇翅盘细胞的生存刽子手半胱天冬酶激活有助于组织再生。通过RNAi筛选，我们确定了akt1和以前未表征的果蝇基因CG8108，这是同源的人类基因CIZ1，从刽子手caspase激活的生存是必不可少的。我们还表明，表达激活的癌基因的细胞经历凋亡caspase激活，Akt1和dCIZ1是它们的生存和过度生长所必需的。因此，执行者半胱天冬酶激活后的存活是一种正常的组织修复机制，被篡夺以促进癌基因驱动的过度生长。虽然执行者半胱天冬酶激活被认为是终端，一些细胞能够存活，这表明额外的调节。在这里，作者表明，果蝇翅成虫盘中的细胞通过Akt1和dCIZ1的caspase激活而存活，并积极参与组织再生。
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. Although executioner caspase activation is considered terminal, some cells are capable of survival, suggesting additional regulation. Here, the authors show that cells in the Drosophila wing imaginal disc survive caspase activation via Akt1 and dCIZ1 and actively participate in tissue regeneration.
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影响因子：
7.7
作者：
Bunker BD;Nellimoottil TT;Boileau RM;Classen AK;Bilder D
通讯作者：
Bilder D
影响因子：
11.8
作者：
Arama, E;Agapite, J;Steller, H
通讯作者：
Steller, H
影响因子：
--
作者：
Blanco E;Ruiz-Romero M;Beltran S;Bosch M;Punset A;Serras F;Corominas M
通讯作者：
Corominas M
影响因子：
7.7
作者：
Bonner C;Bacon S;Concannon CG;Rizvi SR;Baquié M;Farrelly AM;Kilbride SM;Dussmann H;Ward MW;Boulanger CM;Wollheim CB;Graf R;Byrne MM;Prehn JH
通讯作者：
Prehn JH
影响因子：
2.5
作者：
de Beco, Simon;Ziosi, Marcello;Johnston, Laura A.
通讯作者：
Johnston, Laura A.