RGD Reference Report - Metabolic regulation of apoB mRNA editing is associated with phosphorylation of APOBEC-1 complementation factor. - Rat Genome Database

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Metabolic regulation of apoB mRNA editing is associated with phosphorylation of APOBEC-1 complementation factor.

Authors: Lehmann, DM  Galloway, CA  Sowden, MP  Smith, HC 
Citation: Lehmann DM, etal., Nucleic Acids Res. 2006 Jul 4;34(11):3299-308. Print 2006.
RGD ID: 9587738
Pubmed: PMID:16820530   (View Abstract at PubMed)
PMCID: PMC1500872   (View Article at PubMed Central)
DOI: DOI:10.1093/nar/gkl417   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
mRNA editing complex  IDA 9587738 RGD 

Objects Annotated

Genes (Rattus norvegicus)
A1cf  (APOBEC1 complementation factor)


Additional Information