CLONING, CHARACTERIZATION AND EXPRESSION OF 2 XENOPUS BCL-2-LIKE CELL-SURVIVAL GENES

We describe two cloned cDNAs, termed xR1 and xR11, isolated from a Xen opus laevis stage 28-30 embryonic head cDNA library. Comparison of ami no acid (aa) sequences derived from nucleotide (nt) sequences of xR1 a nd xR11 cDNAs revealed substantial homology with bcl-2-related genes, especially with bcl-x(L). In particular, there was a marked conservati on of the BH1 and BH2 domains considered to be important for the anti- cell death and heterodimerisation properties of bcl-2. Constitutive ex pression of xR11 in cultured rat fibroblast (Rat-1) cells conferred a strong protection against cell death induced by the cytotoxic agents s taurosporine and cycloheximide, by serum deprivation and specific dere gulation of c-myc. Measurement of xR1 and xR11 mRNAs by RNase protecti on assay revealed similar widespread expression in Xenopus embryos and tadpoles. Except for an abrupt increase in the accumulation of xR1 an d xR11 mRNAs in brains of mid-metamorphic and post-metamorphic tadpole s and adults, there was insignificant modulation of their expression i n tissues undergoing total regression (tail) or morphogenesis (limb) d uring natural or thyroid hormone-induced metamorphosis. These findings raise the possibility of continuing expression of cell survival genes in tissues undergoing total regression during post-embryonic developm ent.