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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, Zhenming
  • Fulop, Zsolt
  • Wu, Guikai
  • Pone, Egest J
  • Zhang, Jinsong
  • Mai, Thach
  • Thomas, Lisa M
  • Al-Qahtani, Ahmed
  • White, Clayton A
  • Park, Seok-Rae
  • Steinacker, Petra
  • Li, Zenggang
  • Yates, John
  • Herron, Bruce
  • Otto, Markus
  • Zan, Hong
  • Fu, Haian
  • Casali, Paolo
  • et al.

Published Web Location Commons 'BY' version 4.0 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 (Smu-->Sgamma1, Smu-->Sgamma3 or Smu-->Salpha). Moreover, blocking 14-3-3 by difopein, 14-3-3gamma deficiency or expression of a dominant-negative 14-3-3sigma 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.

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