Functional characterization of APOBEC-1 complementation factor phosphorylation sites

被引:10
作者
Lehmann, David M.
Galloway, Chad A.
MacElrevey, Celeste
Sowden, Mark P.
Wedekind, Joseph E.
Smith, Harold C.
机构
[1] Univ Rochester, Dept Biochem & Biophys, Rochester, NY 14642 USA
[2] Univ Rochester, Dept Pathol & Lab Med, Rochester, NY 14642 USA
[3] Univ Rochester, Dept Toxicol, Rochester, NY 14642 USA
[4] Univ Rochester, Environm Hlth Sci Ctr, Rochester, NY 14642 USA
[5] Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY 14642 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | 2007年 / 1773卷 / 03期
关键词
apoB; RNA editing; APOBEC-1 complementation factor; phosphorylation; regulation;
D O I
10.1016/j.bbamcr.2006.11.019
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
ApoB mRNA editing involves site-specific deamination of cytidine 6666 producing an in-frame translation stop codon. Editing minimally requires APOBEC-1 and APOBEC-1 complementation factor (ACF). Metabolic stimulation of apoB mRNA editing in hepatocytes is associated with serine phosphorylation of ACF localized to editing competent, nuclear 27S editosomes. We demonstrate that activation of protein kinase C (PKC) stimulated editing and enhanced ACF phosphorylation in rat primary hepatocytes. Conversely, activation of protein kinase A (PKA) had no effect on editing. Recombinant PKC efficiently phosphorylated purified ACF64 protein in vitro, whereas PKA did not. Mutagenesis of predicted PKC phosphorylation sites S154 and S368 to alanine inhibited ethanol-stimulated induction of editing suggesting that these sites function in the metabolic regulation of editing. Consistent with this interpretation, substitution of S154 and S368 with aspartic acid stimulated editing to levels comparable to ethanol treatment in control McArdle RH7777 cells. These data suggest that phosphorylation of ACF by PKC may be a key regulatory mechanism of apoB mRNA editing in rat hepatocytes. (c) 2006 Elsevier B.V. All rights reserved.
引用
收藏
页码:408 / 418
页数:11
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