Metabolic regulation of ApoB mRNA editing is associated with phosphorylation of APOBEC-1 complementation factor
Open Access
- 28 June 2006
- journal article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 34 (11), 3299-3308
- https://doi.org/10.1093/nar/gkl417
Abstract
Apolipoprotein B (apoB) mRNA editing is a nuclear event that minimally requires the RNA substrate, APOBEC-1 and APOBEC-1 Complementation Factor (ACF). The co-localization of these macro-molecules within the nucleus and the modulation of hepatic apoB mRNA editing activity have been described following a variety of metabolic perturbations, but the mechanism that regulates editosome assembly is unknown. APOBEC-1 was effectively co-immunoprecipitated with ACF from nuclear, but not cytoplasmic extracts. Moreover, alkaline phosphatase treatment of nuclear extracts reduced the amount of APOBEC-1 co-immunoprecipitated with ACF and inhibited in vitro editing activity. Ethanol stimulated apoB mRNA editing was associated with a 2- to 3-fold increase in ACF phosphorylation relative to that in control primary hepatocytes. Significantly, phosphorylated ACF was restricted to nuclear extracts where it co-sedimented with 27S editing competent complexes. Two-dimensional phosphoamino acid analysis of ACF immunopurified from hepatocyte nuclear extracts demonstrated phosphorylation of serine residues that was increased by ethanol treatment. Inhibition of protein phosphatase I, but not PPIIA or IIB, stimulated apoB mRNA editing activity coincident with enhanced ACF phosphorylation in vivo. These data demonstrate that ACF is a metabolically regulated phosphoprotein and suggest that this post-translational modification increases hepatic apoB mRNA editing activity by enhancing ACF nuclear localization/retention, facilitating the interaction of ACF with APOBEC-1 and thereby increasing the probability of editosome assembly and activity.Keywords
This publication has 55 references indexed in Scilit:
- The apolipoprotein B mRNA editing complex performs a multifunctional cycle and suppresses nonsense-mediated decayThe EMBO Journal, 2003
- Two Proteins Essential for Apolipoprotein B mRNA Editing Are Expressed from a Single Gene through Alternative SplicingPublished by Elsevier BV ,2002
- Commitment of apolipoprotein B RNA to the splicing pathway regulates cytidine-to-uridine editing-site utilizationBiochemical Journal, 2001
- Phosphorylation is a regulatory mechanism in apolipoprotein B mRNA editingBiochemical Journal, 2001
- Calcium Increases Apolipoprotein B mRNA EditingBiochemical and Biophysical Research Communications, 2000
- Induction of Cytidine to Uridine Editing on Cytoplasmic Apolipoprotein B mRNA by Overexpressing APOBEC-1Published by Elsevier BV ,2000
- Ethanol Increases Apolipoprotein B mRNA Editing in Rat Primary Hepatocytes and McArdle CellsBiochemical and Biophysical Research Communications, 1998
- Escherichia coli cytidine deaminase provides a molecular model for ApoB RNA editing and a mechanism for RNA substrate recognitionJournal of Molecular Biology, 1998
- Partial Characterization of the Auxiliary Factors Involved in Apolipoprotein B mRNA Editing through APOBEC-1 Affinity ChromatographyPublished by Elsevier BV ,1997
- Identification of high levels of protein phosphatase‐1 in rat liver nucleiFEBS Letters, 1986