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Open Access Publications from the University of California

14-3-3 adaptor proteins recruit AID to 5'-AGCT-3'-rich switch regions for class switch recombination

  • Author(s): Xu, Z
  • Fulop, Z
  • Wu, G
  • Pone, EJ
  • Zhang, J
  • Mai, T
  • Thomas, LM
  • Al-Qahtani, A
  • White, CA
  • Park, SR
  • Steinacker, P
  • Li, Z
  • Yates, J
  • Herron, B
  • Otto, M
  • Zan, H
  • Fu, H
  • Casali, P
  • et al.

Published Web Location Commons Attribution 4.0 International Public License

Class switch DNA recombination (CSR) is the mechanism that diversifies the biological effector functions of antibodies. Activation-induced cytidine deaminase (AID), a key protein in CSR, targets immunoglobulin H (IgH) switch regions, which contain 5'-AGCT-3' repeats in their core. How AID is recruited to switch regions remains unclear. Here we show that 14-3-3 adaptor proteins have an important role in CSR. 14-3-3 proteins specifically bound 5'-AGCT-3' repeats, were upregulated in B cells undergoing CSR and were recruited with AID to the switch regions that are involved in CSR events (Sμ→Sγ1, Sμ→Sγ3 or Sμ→Sa). Moreover, blocking 14-3-3 by difopein, 14-3-3g deficiency or expression of a dominant-negative 14-3-3α mutant impaired recruitment of AID to switch regions and decreased CSR. Finally, 14-3-3 proteins interacted directly with AID and enhanced AID-mediated in vitro DNA deamination, further emphasizing the important role of these adaptors in CSR. © 2010 Nature America, Inc. All rights reserved.

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