Functional conservation of 14-3-3 isoforms in inhibiting Bad-induced apoptosis

14-3-3 proteins are a family of homologous eukaryotic molecules with seven distinct isoforms in mammalian cells. Isoforms of 14-3-3 proteins interact with diverse ligands and are involved in the regulation of mitogenesis, cel l cycle progression, and apoptosis. However, whether different 14-3-3 isofo rms are responsible for distinct functions remains elusive. Here we report that multiple isoforms of 14-3-3 proteins were capable of binding to severa l ligands, Bad, Raf-1, and Cbl. In a functional assay of 14-3-3 isoforms, a ll mammalian 14-3-3 isoforms could inhibit Bad-induced apoptosis. Thus, 14- 3-3 function in regulating one of its ligands, Bad, is conserved among mamm alian isoforms. We addressed whether 14-3-3 isoforms are differentially exp ressed in tissues, which may in part determine isoform-specific interaction s. In situ hybridization revealed that 14-3-3 zeta was present in most tiss ues tested, but sigma was preferentially expressed in epithelial cells. Thu s, isoforms of 14-3-3 can interact and control the function of selected pro tein ligands, and differential tissue distribution of 14-3-3 isoforms may c ontribute to their specific interactions and subsequent downstream signalin g events. (C) 2001 Academic Press.