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.