Differential regulation of splicing, localization and stability of mammalian ARD1235 and ARD1225 isoforms

ARD1 protein is a mammalian gene product homologous to a yeast Ard1p (Arrest defective 1 protein) acetyltransferase. Although two alternative splicing products of ARD1, ARD1235 and ARD1225, were reported in mouse, only ARD1235 orthologue was reported in humans. Here we show that ARD1225 is not expressed in humans, suggesting that factors regulating alternative splicing of ARD1 may have evolved differently between species. In human cells, hARD1235 is shown to be present in both nucleus and cytoplasm. However, in mouse cells, mARD1235 and mARD1225 proteins are localized to the nucleus and cytoplasm, respectively. Moreover, during apoptosis, ARD1235 and ARD1225 isoforms are destabilized by different mechanisms in a species-specific manner and dependent on destabilizing reagents. These results indicate that ARD1235 and ARD1225 isoforms may have different activities and function in different subcellular compartments of mammalian cells.