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

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
September 2010
Nature Structural & Molecular Biology;Sep2010, Vol. 17 Issue 9, p1124
Academic Journal
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 (S??S?1, S??S?3 or S??S?). Moreover, blocking 14-3-3 by difopein, 14-3-3? deficiency or expression of a dominant-negative 14-3-3? 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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