title: Zinc-binding domain-dependent, deaminase-independent actions of apolipoprotein B mRNA-editing enzyme, catalytic polypeptide 2 (Apobec2), mediate its effect on zebrafish retina regeneration.
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 the zinc-binding domain of Apobec2 diminished its ability to stimulate Pou6f2 binding to DNA, and knockdown of Ubc9 or Pou6f2 suppressed retina regeneration.
authors.affiliation: From the Molecular and Behavioral Neuroscience Institute and Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109.
authors.forename: Curtis
authors.initials: C
authors.lastname: Powell
authors.affiliation: From the Molecular and Behavioral Neuroscience Institute and Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109.
authors.forename: Eli
authors.initials: E
authors.lastname: Cornblath
authors.affiliation: From the Molecular and Behavioral Neuroscience Institute and Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109 neuroman@umich.edu.
authors.forename: Daniel
authors.initials: D
authors.lastname: Goldman
mesh_terms: D000071478:APOBEC Deaminases; D000071479:APOBEC-1 Deaminase; D000818:Animals; D030801:Animals, Genetically Modified; D003564:Cytidine Deaminase / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D006801:Humans; D009124:Muscle Proteins / Q000378:metabolism*; D009154:Mutation; D009841:Oligonucleotides / Q000737:chemistry; D050809:POU Domain Factors / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D012038:Regeneration; D012160:Retina / Q000502:physiology*; D058207:Sumoylation; D020798:Two-Hybrid System Techniques; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D015027:Zebrafish; D015032:Zinc; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D009124:Muscle Proteins; D009841:Oligonucleotides; D050809:POU Domain Factors; C098906:POU6F2 protein, human; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; D000071478:APOBEC Deaminases; C120388:APOBEC2 protein, human; D003564:Cytidine Deaminase; D000098843:Ubiquitin-Conjugating Enzyme UBC9; D015032:Zinc
keywords: Apobec; Cytidine Deaminase; Müller Glia; Pou6f2; Regeneration; Retina; Topors; Ubc9; Vision; Zebrafish