Amino-terminal phosphorylation of activation-induced cytidine deaminase suppresses c-myc/IgH translocation


  • A. Gazumyan
  • K. Timachova
  • G. Yuen
  • E. Siden
  • M. Di Virgilio
  • E.M. Woo
  • B.T. Chait
  • B. Reina San-Martin
  • M.C. Nussenzweig
  • K.M. McBride


  • Molecular and Cellular Biology


  • Mol Cell Biol 31 (3): 442-429


  • Activation-induced cytidine deaminase (AID) is a mutator enzyme that initiates class switch recombination and somatic hypermutation of immunoglobulin genes (Ig) in B lymphocytes. However, AID also produces off-target DNA damage, including mutations in oncogenes and double-stranded breaks that can serve as substrates for oncogenic chromosomal translocations. AID is strictly regulated by a number of mechanisms, including phosphorylation at serine 38 and threonine 140, which increase activity. Here we show that phosphorylation can also suppress AID activity in vivo. Serine 3 is a novel phospho-acceptor which, when mutated to alanine, leads to increased class switching and c-myc/IgH translocations without affecting AID levels or catalytic activity. Conversely, increasing AID phosphorylation specifically on serine 3 by interfering with serine/threonine protein phosphatase 2A (PP2A) leads to decreased class switching. We conclude that AID activity and its oncogenic potential can be downregulated by phosphorylation of serine 3 and that this process is controlled by PP2A.