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, ARD1(235) and ARD1(225), were reported in mouse, only ARD1(235) orthologue was reported in humans. Here we show that ARD1(225) is not expressed in humans, suggesting that factors regulating alternative splicing of ARD1 may have evolved differently between species. In human cells, hARD1(235) is shown to be present in both nucleus and cytoplasm. However, in mouse cells, mARD1(235) and mARD1(225) proteins are localized to the nucleus and cytoplasm, respectively. Moreover, during apoptosis, ARD1(235) and ARD1(225) isoforms are destabilized by different mechanisms in a species-specific manner and dependent on destabilizing reagents. These results indicate that ARD1(235) and ARD1(225) isoforms may have different activities and function in different subcellular compartments of mammalian cells.
Chun
Kwang-Hoon
KH
Division of Pharmaceutical Biosciences, College of Pharmacy, The Research Institute for Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Cho
Seung-Ju
SJ
Choi
Joon-Seok
JS
Kim
Se-Hee
SH
Kim
Kyu-Won
KW
Lee
Seung-Ki
SK
D000123:Acetyltransferases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D004795:Enzyme Stability; D005786:Gene Expression Regulation / Q000502:physiology*; D042822:Genomic Instability / Q000235:genetics; D006801:Humans; D051379:Mice; D063209:N-Terminal Acetyltransferase A; D063213:N-Terminal Acetyltransferase E; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D013347:Subcellular Fractions / Q000378:metabolism*
D020033:Protein Isoforms; D000123:Acetyltransferases; D063209:N-Terminal Acetyltransferase A; C504824:NAA10 protein, human; D063213:N-Terminal Acetyltransferase E