Candidate tumour suppressor LUCA-15 can regulate multiple apoptotic pathways.
Functional screening of a human bone marrow cDNA library for suppressors of CD95-mediated apoptosis has led to the identification of a 326 bp fragment (Je2), which not only suppresses CD95-induced apoptosis in Jurkat T-cells, but maps to 3p21.3, to an intronic region of the candidate TSG LUCA-15 locus. Here we report that overexpression of Je2 in CEM-C7 T-cell line is able to suppress CD95-mediated apoptosis, and apoptosis induced by TNFalpha and the glucocorticoid analogue dexamethasone, but was not able to suppress death induced by the topoisomerase II inhibitor etoposide. Je2 inhibition of apoptosis is also associated with a change in the pattern of expression of LUCA-15-encoded proteins. Je2 might therefore function to inhibit apoptosis by destabilising message expression of LUCA-15 and promoting the degradation of its RNA and protein. This suppression of apoptosis by Je2 also appears to be associated with up-regulation of the apoptosis inhibitory protein Bcl-x(L). This study confirms that Je2 is a selective inhibitor of cell death and further implicates LUCA-15 gene locus in the control of apoptosis.
School of Life Sciences, Keele University, Keele, ST5 5BG, UK.
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Mourtada-Maarabouni
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Sutherland
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Williams
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D003907:Dexamethasone / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D005057:Eukaryotic Cells / Q000187:drug effects / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D016147:Genes, Tumor Suppressor / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D016601:RNA-Binding Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D051020:bcl-X Protein; D019014:fas Receptor / Q000187:drug effects / Q000235:genetics
C494811:BCL2L1 protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C473448:RBM5 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014409:Tumor Necrosis Factor-alpha; D025521:Tumor Suppressor Proteins; D051020:bcl-X Protein; D019014:fas Receptor; D005047:Etoposide; D003907:Dexamethasone