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LUCA-15 suppresses CD95-mediated apoptosis in Jurkat T cells

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A Corrigendum to this article was published on 15 January 2004

Abstract

The candidate tumour suppressor gene, LUCA-15, maps to the lung cancer tumour suppressor locus 3p21.3. Overexpression of an alternative RNA splice variant of LUCA-15 has been shown to retard human Jurkat T cell proliferation and to accelerate CD95-mediated apoptosis. An antisense cDNA to the 3′-UTR of this splice variant was able to suppress CD95-mediated apoptosis. Here, we report that overexpression of LUCA-15 itself suppresses CD95-mediated apoptosis in Jurkat cells. This suppression occurs prior to the final execution stage of the CD95 signalling pathway, and is associated with up-regulation of the apoptosis inhibitory protein Bcl-2. LUCA-15 overexpression is also able to inhibit apoptosis induced by the protein kinase inhibitor staurosporine, but is not able to significantly suppress apoptosis mediated by the topoisomerase II inhibitor etoposide. These findings suggest that LUCA-15 is a selective inhibitor of cell death, and confirm the importance of the LUCA-15 genetic locus in the control of apoptosis.

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Acknowledgements

The authors thank Thomas Rothstein for useful advice and critical reading of the manuscript, Ann Stanley for densitometric analysis, and Marty Hansell for graphical assistance. Funding was provided by a PennState Geisinger Cancer Center Research Grant (to LC Sutherland), Contract No. NO1-CO-56000 from the National Cancer Institute, National Institutes of Health (to M Lerman), and the National Institutes of Health DK46778 and M01 RR10732, and the Four Diamonds Fund (to BA Miller). The content of the publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

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Authors and Affiliations

  1. The Henry Hood Research Program, Sigfried and Janet Weis Center for Research, Geisinger Clinic, Danville, 17822-2616, USA

    Leslie C Sutherland & Barbara A Miller

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

    Leslie C Sutherland & Barbara A Miller

  3. Laboratory of Immunobiology, NCI, FCRDC, Frederick, 21702, Maryland, MD, USA

    Michael Lerman

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

    Gwyn T Williams

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  1. Leslie C Sutherland
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  2. Michael Lerman
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Sutherland, L., Lerman, M., Williams, G. et al. LUCA-15 suppresses CD95-mediated apoptosis in Jurkat T cells. Oncogene 20, 2713–2719 (2001). https://doi.org/10.1038/sj.onc.1204371

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  • DOI: https://doi.org/10.1038/sj.onc.1204371

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