期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
卷 1773, 期 3, 页码 408-418出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamcr.2006.11.019
关键词
apoB; RNA editing; APOBEC-1 complementation factor; phosphorylation; regulation
资金
- NCRR NIH HHS [RR15934] Funding Source: Medline
- NIDDK NIH HHS [R01 DK043739, DK43739] Funding Source: Medline
- NIEHS NIH HHS [5T32 ES07026, T32 ES007026] Funding Source: Medline
- NIGMS NIH HHS [R01 GM063162, T32 GM068411, 5T32 GM068411, GM63162] Funding Source: Medline
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.
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