title: Bicaudal is a conserved substrate for Drosophila and mammalian caspases and is essential for cell survival.
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.
authors.affiliation: Molecular Cell Biology Laboratory, Department of Genetics, Smurfit Institute, Trinity College, Dublin, Ireland [corrected]
authors.forename: Emma M
authors.initials: EM
authors.lastname: Creagh
authors.forename: Gabriela
authors.initials: G
authors.lastname: Brumatti
authors.forename: Clare
authors.initials: C
authors.lastname: Sheridan
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Duriez
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Taylor
authors.forename: Sean P
authors.initials: SP
authors.lastname: Cullen
authors.forename: Colin
authors.initials: C
authors.lastname: Adrain
authors.forename: Seamus J
authors.initials: SJ
authors.lastname: Martin