Intracellular Trafficking Determinants in APOBEC-1, the Catalytic Subunit for Cytidine to Uridine Editing of Apolipoprotein B mRNA

Abstract

The posttranscriptional deamination editing of apolipoprotein B (apoB) mRNA catalyzed by APOBEC-1 (apoB mRNA $\text{e}$diting $\text{c}$atalytic subunit $\text{1}$) is a nuclear process. The signals in APOBEC-1 responsible for its dual cytoplasmic/nuclear distribution have been evaluated. Residues 97–172 in the middle of APOBEC-1 together with its N-terminal 56 residues affect nuclear localization. Mutagenesis studies however revealed no discrete nuclear localization signal in APOBEC-1. Fifteen amino acids (Leu 173–Leu 187) within the previously identified C-terminal domain of APOBEC-1 were sufficient as a determinant for cytoplasmic distribution in that context. These residues failed to demonstrate nuclear export function in a reporter assay. Further, the distribution of APOBEC-1 in the cytoplasm did not respond to leptomycin B, suggesting that APOBEC-1 did not have nuclear export activity. The data suggested that there are at least three regions in APOBEC-1 that participate in its distribution in both the nucleus and the cytoplasm of editing competent cells; however, none of these meet the functional criteria of nuclear localization or nuclear export signals. The findings are discussed in terms of their implications in the regulation of nuclear editing activity and the possibility that interactions with chaperones may play a role in the cellular distribution of APOBEC-1.