Different subcellular localizations and functions of human ARD1 variants

Seo,Ji Hae; Park,Ji-Hyeon; Lee,Eun Ji; Kim,Kyu-Won

doi:10.3892/ijo.2014.2770

Different subcellular localizations and functions of human ARD1 variants

Authors:
- Ji Hae Seo
- Ji-Hyeon Park
- Eun Ji Lee
- Kyu-Won Kim
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Affiliations: SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea
Published online on: November 21, 2014 https://doi.org/10.3892/ijo.2014.2770
Pages: 701-707

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Abstract

ARD1 is present in various species and has several variants derived from alternative splicing of mRNA. Previously, we reported differential biological functions and cellular distributions of mouse ARD1 (mARD1) variants. However, in comparison to mARD1 variants, human ARD1 (hARD1) variants have been rarely studied. In this study, we characterized a hARD1 variant, hARD1131 and investigated its cellular activities. hARD1131 mRNA was isolated from HeLa cells and sequenced. Sequence alignment revealed that, compared to hARD1235, the most common form of hARD1, the mRNA sequence encoding hARD1131 possesses an altered reading frame due to a 46-bp deletion. Thus, hARD1131 and hARD1235 differ in their C-terminal regions with a partially deleted acetyltransferase domain at the C-terminus of hARD1131. Moreover, hARD1131 and hARD1235 showed different subcellular localizations and biological functions. hARD1131 was mostly localized in the cell nucleus, whereas hARD1235 was primarily localized in the cytoplasm. In addition, hARD1235 stimulated cell proliferation by upregulation of cyclin D1, however hARD1131 had no influence on cyclin D1 expression and cell growth. Because hARD1235 enhances cell proliferation by its autoacetylation activity, we examined the autoacetylation activity of hARD1131 and observed that this function was absent in hARD1131. These results suggest that human ARD1 variants have different effects on cell proliferation, which may result from distinct subcellular localizations and autoacetylation activities.

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