Skip to main content
eScholarship
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

https://doi.org/10.1038/nsmb.1884Creative Commons Attribution 4.0 International Public License
Abstract

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.

Many UC-authored scholarly publications are freely available on this site because of the UC Academic Senate's Open Access Policy. Let us know how this access is important for you.

Main Content
Current View