例如:"lncRNA", "apoptosis", "WRKY"

Zinc-binding domain-dependent, deaminase-independent actions of apolipoprotein B mRNA-editing enzyme, catalytic polypeptide 2 (Apobec2), mediate its effect on zebrafish retina regeneration.

J Biol Chem. 2014 Oct 17;289(42):28924-41. Epub 2014 Sep 04
Curtis Powell 1 , Eli Cornblath 1 , Daniel Goldman 2
Curtis Powell 1 , Eli Cornblath 1 , Daniel Goldman 2

[No authors listed]

Author information
  • 1 From the Molecular and Behavioral Neuroscience Institute and Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109.
  • 2 From the Molecular and Behavioral Neuroscience Institute and Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109 neuroman@umich.edu.

摘要


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.

KEYWORDS: Apobec, Cytidine Deaminase, Müller Glia, Pou6f2, Regeneration, Retina, Topors, Ubc9, Vision, Zebrafish