Alterations of SAG mRNA in human cancer cell lines: requirement for the RING finger domain for apoptosis protection.

We have recently cloned and characterized a novel zinc RING finger gene, SAG (sensitive to apoptosis gene). SAG has antioxidant activity and protects cells from apoptosis induced by metal ions and redox compounds. During the course of SAG cloning, we identified two forms of deletions of SAG mRNA in colon and testicular carcinoma cell lines. The first form (SAG-MU1) consists of a 7 bp deletion that results in a frameshift and abolishes the RING finger domain. The second (SAG-MU2) consists of an in-frame 48 bp deletion that truncates 16 amino acids in the protein but retains the RING finger domain. Functional studies using stable transfectant lines reveal that, like wild-type SAG, SAG-MU2 retains anti-apoptosis activity, whereas SAG-MU1 shows no such protection. The results indicate that the C-terminal zinc RING finger domain is required for anti-apoptosis activity of SAG.