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Regulation of apoptosis by fau revealed by functional expression cloning and antisense expression

Oncogene volume 23, pages 9419–9426 (2004)Cite this article

Abstract

Functional expression cloning is a powerful strategy for identifying critical steps in biological pathways independently of prior assumptions. It is particularly suitable for the identification of molecules crucial to the control of apoptosis. Our screen for sequences suppressing T-cell apoptosis isolated a sequence antisense to fau (Finkel–Biskis–Reilly murine sarcoma virus (FBR-MuSV)-associated ubiquitously expressed gene). The fox gene in FBR murine osteosarcoma virus is also antisense to fau and several reports have indicated that fau displays tumour suppressor and oncogenic properties in different contexts. Our observations indicate that the fau antisense sequence suppresses expression of endogenous fau mRNA and produces resistance to apoptosis induced both by the glucocorticoid analogue dexamethasone' by ultraviolet radiation, and by the anticancer drug cisplatin. In all cases, colony-forming ability is protected, indicating that fau affects the critical events prior to commitment to cell death. Overexpression of fau in the sense orientation induces cell death, which is inhibited both by Bcl-2 and by inhibition of caspases, in line with its proposed role in apoptosis.

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Acknowledgements

We thank the Wellcome Trust for financial support, Dr Morihiko Nakamura for generously providing anti-Fau antibody, Dr David Askew for SFFV-neo-bcl2, Dr Janet Meredith for subcloning DG3.cd1, Dr Derric Nimmo for help with photography and the Dead Cell Lab and our collaborators at WEHI, Melbourne and the Hanson Institute, Adelaide for warm hospitality, help and advice.

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Authors and Affiliations

  1. School of Life Sciences, Keele University, Keele, ST5 5BG, UK

    Mirna Mourtada-Maarabouni, Lucy Kirkham & Gwyn T Williams

  2. Molecular Medicine, Rayne Institute, GKT School of Medicine, King's Denmark Hill Campus, 123 Coldharbour Lane, London, SE21 7AN, UK

    Farzin Farzaneh

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Correspondence to Mirna Mourtada-Maarabouni or Gwyn T Williams.

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Mourtada-Maarabouni, M., Kirkham, L., Farzaneh, F. et al. Regulation of apoptosis by fau revealed by functional expression cloning and antisense expression. Oncogene 23, 9419–9426 (2004). https://doi.org/10.1038/sj.onc.1208048

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