Cytoplasmic activation-induced cytidine deaminase (AID) exists in stoichiometric complex with translation elongation factor 1α (eEF1A)

Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18366-71. doi: 10.1073/pnas.1106729108. Epub 2011 Oct 31.

Abstract

Activation-induced cytidine deaminase (AID) is a B lymphocyte-specific DNA deaminase that acts on the Ig loci to trigger antibody gene diversification. Most AID, however, is retained in the cytoplasm and its nuclear abundance is carefully regulated because off-target action of AID leads to cancer. The nature of the cytosolic AID complex and the mechanisms regulating its release from the cytoplasm and import into the nucleus remain unknown. Here, we show that cytosolic AID in DT40 B cells is part of an 11S complex and, using an endogenously tagged AID protein to avoid overexpression artifacts, that it is bound in good stoichiometry to the translation elongation factor 1 alpha (eEF1A). The AID/eEF1A interaction is recapitulated in transfected cells and depends on the C-terminal domain of eEF1A (which is not responsible for GTP or tRNA binding). The eEF1A interaction is destroyed by mutations in AID that affect its cytosolic retention. These results suggest that eEF1A is a cytosolic retention factor for AID and extend on the multiple moonlighting functions of eEF1A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AICDA (Activation-Induced Cytidine Deaminase)
  • Animals
  • Cell Line
  • Chickens
  • Cytidine Deaminase / metabolism*
  • Cytoplasm / enzymology*
  • Peptide Elongation Factor 1 / metabolism*
  • Protein Binding

Substances

  • Peptide Elongation Factor 1
  • AICDA (Activation-Induced Cytidine Deaminase)
  • Cytidine Deaminase