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

2026

The ARD1²³⁵ and ARD1²²⁵ protein isoforms result from alternative splicing of a mammalian gene product homologous to a yeast acetyltransferase, Ard1p (Arrest defective 1 protein). Human and mouse ARD1²³⁵ transfers an acetyl group to the α-amino group of target proteins by forming a complex with NAT1. Mouse ARD1²²⁵ regulates proteasomal degradation of hypoxia-inducible factor 1 alpha (HIF-1α). Here we report that splicing of ARD1 differs between mouse and primates, suggesting that factors regulating alternative splicing of ARD1 may have evolved differently in the mouse. In human cells, hARD1²³⁵ are shown to be present in both nucleus and cytoplasm. Interestingly, 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.