AN ADDITIONAL FORM OF RAT BCL-X, BCL-X-BETA, GENERATED BY AN UNSPLICED RNA, PROMOTES APOPTOSIS IN PROMYELOID CELLS

The bcl-2 oncogene product delays apoptotic cell death and prolongs th e cell survival, We cloned two bcl-2-related cDNAs from a rat thymus c DNA library by low stringency hybridization with a rat bcl-2 fragment as a probe. One of these, designated bcl-x alpha, was a counterpart of the human bcl-x(L) reported previously as a bcl-2-related gene (Boise , L. H., Gonzalez-Garcia, M., Postema, C. E., Ding, L., Lindsten, T., Turka, L. A., Mao, M., Nunez, G., and Thompson, C. B. (1993) Cell 74, 597-608). The other, designated bcl-x beta, was novel and found to be generated by an unspliced mRNA, whereas bcl-x alpha was generated from a spliced transcript. The splice junction exactly corresponded to tha t found in the bcl-2 gene. bcl-x beta was specifically expressed in ce rebellum, heart, and thymus. When bcl-x beta directed by a strong prom oter was introduced into an interleukin-3-dependent promyeloid cell li ne, FDC-P1, DNA fragmentation was observed even in the growing state i n the presence of interleukin-3 although not in the control transfecta nts. This finding suggests that the rat bcl-x beta gene product promot es apoptosis in the promyeloid cells.