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Simultaneous acceleration of the cell cycle and suppression of apoptosis by splice variant delta-6 of the candidate tumour suppressor LUCA-15/RBM5

Mourtada-Maarabouni, Mirna; Sutherland, Leslie C.; Meredith, Janet M.; Williams, Gwyn T.

Authors

Leslie C. Sutherland

Janet M. Meredith

Gwyn T. Williams



Contributors

M. Mourtada-Maarabouni
Other

L.C. Sutherland
Other

J.M. Meredith
Other

G.T. Williams
Other

Abstract

Background: The short arm of chromosome 3 is thought to include one or more tumour suppressor genes (TSGs), since carcinoma of various tissues display deletions in this region. Many genes mapping to this region have recently been identified, including the LUCA-15/RBM5 gene.

Results: In this study we report the cloning from human bone marrow library of a splice variant of LUCA-15 which lacks exon 6, resulting in a frameshift and producing a truncated protein of 150 amino acids instead of 815 amino acids. This variant is widely expressed at a low level in normal tissues and is expressed at increased levels in T-leukaemic cell lines. Over-expression of this splice variant after electroporation both shortened the cell cycle and inhibited CD95-mediated apoptosis in CEM-C7 T-cells. In marked contrast, over-expression of the full length LUCA-15/RBM5 suppressed cell proliferation both by inducing apoptosis and by extending the G1 phase of the cell cycle.

Conclusion: These results, taken together with previous observations from ourselves and others, suggest that LUCA-15 is involved in the control of both apoptosis and the cell cycle. Since oncogenesis often relies on separate changes in molecules regulating apoptosis on the one hand, and proliferation, on the other, the discovery of a candidate tumour suppressor gene which affects both processes simultaneously is likely to be of major significance.

Citation

Mourtada-Maarabouni, M., Sutherland, L. C., Meredith, J. M., & Williams, G. T. (2003). Simultaneous acceleration of the cell cycle and suppression of apoptosis by splice variant delta-6 of the candidate tumour suppressor LUCA-15/RBM5. Genes to Cells, 8(2), 109-119. https://doi.org/10.1046/j.1365-2443.2003.00619.x

Journal Article Type Article
Online Publication Date Feb 12, 2003
Publication Date 2003
Deposit Date May 15, 2024
Journal Genes to Cells
Print ISSN 1356-9597
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 8
Issue 2
Pages 109-119
ISBN 13569597
DOI https://doi.org/10.1046/j.1365-2443.2003.00619.x
Public URL https://keele-repository.worktribe.com/output/543819
Publisher URL https://onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2443.2003.00619.x