Bicaudal is a conserved substrate for Drosophila and mammalian caspases and is essential for cell survival

Emma M Creagh, Gabriela Brumatti, Clare Sheridan, Patrick J Duriez, Rebecca C Taylor, Sean P Cullen, Colin Adrain, Seamus J Martin

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Members of the caspase family of cysteine proteases coordinate cell death through restricted proteolysis of diverse protein substrates and play a conserved role in apoptosis from nematodes to man. However, while numerous substrates for the mammalian cell death-associated caspases have now been described, few caspase substrates have been identified in other organisms. Here, we have utilized a proteomics-based approach to identify proteins that are cleaved by caspases during apoptosis in Drosophila D-Mel2 cells, a subline of the Schneider S2 cell line. This approach identified multiple novel substrates for the fly caspases and revealed that bicaudal/betaNAC is a conserved substrate for Drosophila and mammalian caspases. RNAi-mediated silencing of bicaudal expression in Drosophila D-Mel2 cells resulted in a block to proliferation, followed by spontaneous apoptosis. Similarly, silencing of expression of the mammalian bicaudal homologue, betaNAC, in HeLa, HEK293T, MCF-7 and MRC5 cells also resulted in spontaneous apoptosis. These data suggest that bicaudal/betaNAC is essential for cell survival and is a conserved target of caspases from flies to man.

Original languageEnglish
Pages (from-to)e5055
JournalPLoS ONE
Volume4
Issue number3
DOIs
Publication statusPublished - 2009

Keywords

  • Animals
  • Apoptosis
  • Caspases/metabolism
  • Cell Line
  • Cell Survival
  • Drosophila
  • Drosophila Proteins/metabolism
  • Humans
  • Mammals
  • Proteomics/methods
  • RNA-Binding Proteins/metabolism
  • Species Specificity
  • Substrate Specificity

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