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

Bicaudal is a conserved substrate for Drosophila and mammalian caspases and is essential for cell survival
Bicaudal is a conserved substrate for Drosophila and mammalian caspases and is essential for cell survival
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.
1932-6203
e5055
Creagh, Emma M.
c5311521-65cc-46df-8f7d-d6416aa05a95
Brumatti, Gabriela
87802265-47e9-47ad-b74e-1bb4410fc7cd
Sheridan, Clare
258f2e42-c828-4497-8d5a-9d83a51f73d3
Duriez, Patrick J.
4cf499bc-007a-43b3-b180-d6e5dc3d151b
Taylor, Rebecca C.
72e4edb9-e8bb-47ad-a544-145a50896d23
Cullen, Sean P.
f4ee304e-a1ed-44a8-9588-e0dd30ef6f80
Adrain, Colin
f7950ceb-b788-4d86-a607-b9efc4437142
Martin, Seamus J.
3df02649-5634-44da-834d-098937a7ae5b
Creagh, Emma M.
c5311521-65cc-46df-8f7d-d6416aa05a95
Brumatti, Gabriela
87802265-47e9-47ad-b74e-1bb4410fc7cd
Sheridan, Clare
258f2e42-c828-4497-8d5a-9d83a51f73d3
Duriez, Patrick J.
4cf499bc-007a-43b3-b180-d6e5dc3d151b
Taylor, Rebecca C.
72e4edb9-e8bb-47ad-a544-145a50896d23
Cullen, Sean P.
f4ee304e-a1ed-44a8-9588-e0dd30ef6f80
Adrain, Colin
f7950ceb-b788-4d86-a607-b9efc4437142
Martin, Seamus J.
3df02649-5634-44da-834d-098937a7ae5b

Creagh, Emma M., Brumatti, Gabriela, Sheridan, Clare, Duriez, Patrick J., Taylor, Rebecca C., Cullen, Sean P., Adrain, Colin and Martin, Seamus J. (2009) Bicaudal is a conserved substrate for Drosophila and mammalian caspases and is essential for cell survival. PLoS ONE, 4 (3), e5055. (doi:10.1371/journal.pone.0005055). (PMID:9422513)

Record type: Article

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.

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Published date: 30 March 2009

Identifiers

Local EPrints ID: 164795
URI: http://eprints.soton.ac.uk/id/eprint/164795
ISSN: 1932-6203
PURE UUID: 00a2605c-ea78-4cd4-bc22-68c7ba7836c1
ORCID for Patrick J. Duriez: ORCID iD orcid.org/0000-0003-1814-2552

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Date deposited: 05 Oct 2010 10:01
Last modified: 14 Mar 2024 02:52

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Contributors

Author: Emma M. Creagh
Author: Gabriela Brumatti
Author: Clare Sheridan
Author: Patrick J. Duriez ORCID iD
Author: Rebecca C. Taylor
Author: Sean P. Cullen
Author: Colin Adrain
Author: Seamus J. Martin

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