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LUCA-15-encoded sequence variants regulate CD95-mediated apoptosis

Oncogene volume 19, pages 3774–3781 (2000)Cite this article

Abstract

Using an expression cloning system to discover novel genes involved in apoptosis, we identified a 326 bp bone marrow cDNA fragment (termed Je2) that suppresses, upon transfection, CD95-mediated apoptosis in Jurkat T cells. Sequence homology revealed that Je2 maps to 3p21.3, to an intronic region of the candidate TSG LUCA-15 locus. It represents, in fact, an antisense transcript to the 3′-UTR of two novel splice variants of this gene. Overexpression of sequence representing one of these splice variants (a 2.6 kb cDNA termed Clone 26), inhibited proliferation of Jurkat cells and sensitized them to CD95-mediated apoptosis. This study therefore implicates the LUCA-15 gene locus in the control of apoptosis.

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Acknowledgements

The authors would like to thank Michael Lerman for critical reading of the manuscript, Thomas Rothstein for many helpful discussions and reading of the manuscript, Claire Anderson for invaluable assistance in growing and shipping cells, Vanessa Hedge and David Huen for advice and critical discussions, Margaret Critchlow for technical assistance, and Ian Wright, Marty Hansell and John Harms for graphical assistance. This work has benefited from the use of the SEQNET facility, Daresbury. Funding was provided by the Wellcome Trust, UK, the Medical Research Council, UK, the Cancer Research Campaign, UK, the National Institutes of Health DK46778 and M01 RR10732, and the Four Diamonds Fund.

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Authors and Affiliations

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

    Leslie C Sutherland, Hazel C Cable & Gwyn T Williams

  2. Molecular Carcinogenesis, Haddow Laboratories, Institute of Cancer Research, Sutton, Surrey, SM2 5NG, UK

    Sandra E Edwards & Colin S Cooper

  3. Department of Pediatrics, Division of Hematology/Oncology, The Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, Hershey, Pennsylvania, 17033-0850, PA, USA

    Leslie C Sutherland & Barbara A Miller

  4. Eastern Quebec Peptide Sequencing Facility, Centre de Recherche du CHUL, 2705, Boulevard Laurier, Sainte-Foy, Quebec, G1V 4G2, Canada

    Guy G Poirier

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  1. Leslie C Sutherland
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Sutherland, L., Edwards, S., Cable, H. et al. LUCA-15-encoded sequence variants regulate CD95-mediated apoptosis. Oncogene 19, 3774–3781 (2000). https://doi.org/10.1038/sj.onc.1203720

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  • DOI: https://doi.org/10.1038/sj.onc.1203720

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