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

Nat Commun. 2020 Nov 12;11(1):5726. doi: 10.1038/s41467-020-19068-2.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis
  • Carcinogenesis / genetics*
  • Caspases / metabolism*
  • Cell Death
  • Cell Survival*
  • Drosophila / genetics
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Humans
  • Nuclear Proteins
  • Oncogenes
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA Interference
  • Transcription Factors
  • Wings, Animal
  • Zinc Fingers

Substances

  • Ciz1 protein, human
  • Drosophila Proteins
  • GAL4 protein, Drosophila
  • Nuclear Proteins
  • Transcription Factors
  • AKT1 protein, human
  • Akt1 protein, Drosophila
  • Proto-Oncogene Proteins c-akt
  • Caspases