dUev1a modulates TNF-JNK mediated tumor progression and cell death in Drosophila

Dev Biol. 2013 Aug 15;380(2):211-21. doi: 10.1016/j.ydbio.2013.05.013. Epub 2013 May 29.

Abstract

Loss of cell polarity cooperates with oncogenic Ras to induce JNK-dependent tumor growth and invasion. To identify additional genes that modulate tumor progression, we have performed a genetic screen in Drosophila and found that loss of dUev1a, the ortholog of mammalian Uev1, suppressed lgl(-/-)/Ras(V12) induced JNK-mediated tumor growth and invasion. Furthermore, loss of dUev1a suppressed TNF ortholog Eiger-induced JNK-mediated cell invasion and cell death. Finally, dUev1a cooperated with Bendless to activate JNK signaling through dTRAF2. Together, our data indicate that dUev1a encodes an essential component of the evolutionary conserved TNF-JNK signaling pathway that modulates tumor progression and cell death in metazoan.

Keywords: Cell death; JNK; TNF; Tumor invasion; dUev1a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death
  • Disease Progression
  • Drosophila
  • Drosophila Proteins / physiology*
  • Early Growth Response Transcription Factors / physiology
  • JNK Mitogen-Activated Protein Kinases / physiology*
  • Matrix Metalloproteinase 1 / physiology
  • Neoplasms / etiology*
  • Neoplasms / pathology
  • Signal Transduction / physiology*
  • Transcription Factors / physiology*
  • Tumor Necrosis Factor-alpha / physiology*
  • Ubiquitin-Conjugating Enzymes / physiology*

Substances

  • Drosophila Proteins
  • Early Growth Response Transcription Factors
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • Ubiquitin-Conjugating Enzymes
  • Uev1a protein, Drosophila
  • JNK Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 1