Snail modulates JNK-mediated cell death in Drosophila

Cell Death Dis. 2019 Nov 26;10(12):893. doi: 10.1038/s41419-019-2135-7.

Abstract

Cell death plays a pivotal role in animal development and tissue homeostasis. Dysregulation of this process is associated with a wide variety of human diseases, including developmental and immunological disorders, neurodegenerative diseases and tumors. While the fundamental role of JNK pathway in cell death has been extensively studied, its down-stream regulators and the underlying mechanisms remain largely elusive. From a Drosophila genetic screen, we identified Snail (Sna), a Zinc-finger transcription factor, as a novel modulator of ectopic Egr-induced JNK-mediated cell death. In addition, sna is essential for the physiological function of JNK signaling in development. Our genetic epistasis data suggest that Sna acts downstream of JNK to promote cell death. Mechanistically, JNK signaling triggers dFoxO-dependent transcriptional activation of sna. Thus, our findings not only reveal a novel function and the underlying mechanism of Sna in modulating JNK-mediated cell death, but also provide a potential drug target and therapeutic strategies for JNK signaling-related diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Eye / cytology
  • Eye / metabolism
  • Genes, Dominant
  • Genetic Testing
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Larva / metabolism
  • MAP Kinase Signaling System
  • Phenotype
  • Snail Family Transcription Factors / genetics
  • Snail Family Transcription Factors / metabolism*
  • Transcription, Genetic
  • Wings, Animal / cytology
  • Wings, Animal / metabolism

Substances

  • Drosophila Proteins
  • Snail Family Transcription Factors
  • sna protein, Drosophila
  • JNK Mitogen-Activated Protein Kinases
  • bsk protein, Drosophila