PUBLICATION

Zinc-binding Domain-dependent, Deaminase-independent Actions of Apolipoprotein B mRNA-editing Enzyme, Catalytic Polypeptide 2 (Apobec2), Mediate Its Effect on Zebrafish Retina Regeneration

Authors
Powell, C., Cornblath, E., Goldman, D.
ID
ZDB-PUB-140906-3
Date
2014
Source
The Journal of biological chemistry   289(42): 28924-41 (Journal)
Registered Authors
Goldman, Dan
Keywords
Muller glia, Pou6f2, Topors, Ubc9, apobec, cytidine deaminase, regeneration, retina, vision, zebrafish
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Cytidine Deaminase/metabolism*
  • Gene Expression Regulation, Developmental
  • HEK293 Cells
  • Humans
  • Muscle Proteins/metabolism*
  • Mutation
  • Oligonucleotides/chemistry
  • POU Domain Factors/metabolism
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Regeneration
  • Retina/physiology*
  • Sumoylation
  • Two-Hybrid System Techniques
  • Ubiquitin-Conjugating Enzymes/metabolism
  • Ubiquitin-Protein Ligases/metabolism
  • Zebrafish
  • Zinc
PubMed
25190811 Full text @ J. Biol. Chem.
Abstract
The Apobec/AID family of cytosine deaminases can deaminate cytosine and thereby contribute to adaptive and innate immunity, DNA demethylation and the modification of cellular mRNAs. Unique among this family is Apobec2 whose enzymatic activity has been questioned and whose function remains poorly explored. We recently reported that zebrafish Apobec2a and Apobec2b (Apobec2a,2b) regulate retina regeneration; however, their mechanism of action remained unknown. Here we show that although Apobec2a,2b lack cytosine deaminase activity, they require a conserved zinc-binding domain to stimulate retina regeneration. Interestingly, we found that human APOBEC2 is able to functionally substitute for Apobec2a,2b during retina regeneration. By identifying Apobec2-interacting proteins, including ubiquitin conjugating enzyme 9 (Ubc9), topoisomerase I binding, arginine/serine rich, E3 ubiquitin protein ligase (Toporsa) and POU class 6 homeobox 2 (Pou6f2), we uncovered that sumoylation regulates Apobec2 subcellular localization and that nuclear Apobec2 controls Pou6f2 binding to DNA. Importantly, mutations in Apobec2's zinc-binding domain diminish its ability to stimulate Pou6f2 binding to DNA and knockdown of Ubc9 or Pou6f2 suppressed retina regeneration.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes