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.
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.
Authors: Kazuo Fushimi; Payal Ray; Amar Kar; Lei Wang; Leslie C Sutherland; Jane Y Wu Journal: Proc Natl Acad Sci U S A Date: 2008-10-07 Impact factor: 11.205