SAG, a novel zinc RING finger protein that protects cells from apoptosis induced by redox agents

SAG (sensitive to apoptosis gene) was cloned as an inducible gene by 1,10-p henanthroline (OP), a redoxsensitive compound and an apoptosis inducer. SAG encodes a novel zinc RING finger protein that consists of 113 amino acids with a calculated molecular mass of 12.6 kDa. SAG is highly conserved durin g evolution, with identities of 70% between human and Caenorhabditis elegan s sequences and 55% between human and yeast sequences. In human tissues, SA G is ubiquitously expressed at high levels in skeletal muscles, heart, and testis. SAG is localized in both the cytoplasm and the nucleus of cells, an d its gene was mapped to chromosome 3q22-24. Bacterially expressed and puri fied human SAG binds to zinc and copper metal ions and prevents lipid perox idation induced by copper or a free radical generator. When overexpressed i n several human cell lines, SAG protects cells from apoptosis induced by re dox agents (the metal chelator OP and zinc or copper metal ions). Mechanist ically, SAG appears to inhibit and/or delay metal ion-induced cytochrome c release and caspase activation. Thus, SAG is a cellular protective molecule that appears to act as an antioxidant to inhibit apoptosis induced by meta l ions and reactive oxygen species.