Akt1 and dCIZ1 promote cell survival from apoptotic caspase activation during regeneration and oncogenic overgrowth.

TitleAkt1 and dCIZ1 promote cell survival from apoptotic caspase activation during regeneration and oncogenic overgrowth.
Publication TypeJournal Article
Year of Publication2020
AuthorsSun G, Ding XAustin, Argaw Y, Guo X, Montell DJ
JournalNat Commun
Volume11
Issue1
Pagination5726
Date Published2020 11 12
ISSN2041-1723
Abstract

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.

DOI10.1038/s41467-020-19068-2
Alternate JournalNat Commun
PubMed ID33184261