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


CONCLUSIONS
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.
Mourtada-Maarabouni
Mirna
M
School of Life Sciences, Keele University, Keele, ST5 5BG, UK.
Sutherland
Leslie C
LC
Meredith
Janet M
JM
Williams
Gwyn T
GT
D017398:Alternative Splicing; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins; D002455:Cell Division; D002470:Cell Survival; D002893:Chromosomes, Human, Pair 3; D004268:DNA-Binding Proteins; D016368:Frameshift Mutation; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D016601:RNA-Binding Proteins; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers / Q000235:genetics; D019014:fas Receptor / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C473448:RBM5 protein, human; D016601:RNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D019014:fas Receptor