Published on Feb. 1, 1997 in Genes Dev volume 11(3).

PubMed ID: 9030685

DOI: 10.1101/gad.11.3.321

Abstract:

Transgene expression of the apolipoprotein B mRNA-editing enzyme (APOBEC-1) causesdysplasia and carcinoma in mouse and rabbit livers. Using a modified differentialdisplay technique, we identified a novel mRNA (NAT1 for novel APOBEC-1 target no. 1)that is extensively edited at multiple sites in these livers. The aberrant editingalters encoded amino acids, creates stop codons, and results in markedly reducedlevels of the NAT1 protein in transgenic mouse livers. NAT1 is expressedubiquitously and is extraordinarily conserved among species. It has homology to thecarboxy-terminal portion of the eukaryotic translation initiation factor (eIF) 4Gthat binds eIF4A and eIF4E to form eIF4F. NAT1 binds eIF4A but not eIF4E andinhibits both cap-dependent and cap-independent translation. NAT1 is likely to be afundamental translational repressor, and its aberrant editing could contribute tothe potent oncogenesis induced by overexpression of APOBEC-1.