Multiple protein domains determine the cell type-specific nuclear distribution of the catalytic subunit required for apolipoprotein B mRNA editing.

Abstract

Apolipoprotein B (apoB) mRNA editing catalyzed by apoB mRNA editing catalytic subunit 1 (APOBEC-1) has been proposed to be a nuclear process. To test this hypothesis, the subcellular distribution of hemagglutinin- (HA) tagged APOBEC-1 expressed in transiently transfected hepatoma cells was determined by indirect immunofluorescence microscopy. HA-APOBEC-1 was detected in both the nucleus and cytoplasm of rat and human hepatoma cells. Mutagenesis of APOBEC-1 demonstrated that the N-terminal 56 amino acids (1-56) were necessary for the nuclear distribution of APOBEC-1, but this region did not contain a functional nuclear localization signal (NLS). However, we identified a 24-amino acid domain in the C terminus of APOBEC-1 with characteristics of a cytoplasmic retention signal (CRS) or a nuclear export signal (NES). These data suggest, therefore, that the nuclear import of APOBEC-1 may not be mediated by a positive NLS; rather, it may be achieved by overcoming the effect of a CRS/NES. We also demonstrated that the nuclear distribution of APOBEC-1 occurred only in cell lines that were capable of editing apoB RNA. We propose that the cellular distribution of APOBEC-1 is determined by multiple domains within this protein, and a nuclear localization of the enzyme may be regulated by cell type-specific factors that render these cells uniquely editing competent.

• Authors: Y Yang, Y Yang, H C Smith
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 94 Issue 24 Pg. 13075-80 (Nov 25 1997) ISSN: 0027-8424 [Print] United States
• PMID: 9371802 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Apolipoproteins B
• AICDA (activation-induced cytidine deaminase)
• APOBEC-1 Deaminase
• APOBEC1 protein, human
• Apobec1 protein, rat
• Cytidine Deaminase

Topics

• APOBEC-1 Deaminase
• Amino Acid Sequence
• Animals
• Apolipoproteins B (genetics)
• CHO Cells
• COS Cells
• Catalysis
• Cell Nucleus (metabolism)
• Cricetinae
• Cytidine Deaminase (metabolism)
• Humans
• Molecular Sequence Data
• RNA Editing
• Subcellular Fractions (metabolism)
• Tumor Cells, Cultured