title: 14-3-3 adaptor proteins recruit AID to 5'-AGCT-3'-rich switch regions for class switch recombination.
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 (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.
authors: Institute for Immunology, School of Medicine and School of Biological Sciences, University of California, Irvine, California, USA.
authors: Zhenming
authors: Z
authors: Xu
authors: Zsolt
authors: Z
authors: Fulop
authors: Guikai
authors: G
authors: Wu
authors: Egest J
authors: EJ
authors: Pone
authors: Jinsong
authors: J
authors: Zhang
authors: Thach
authors: T
authors: Mai
authors: Lisa M
authors: LM
authors: Thomas
authors: Ahmed
authors: A
authors: Al-Qahtani
authors: Clayton A
authors: CA
authors: White
authors: Seok-Rae
authors: SR
authors: Park
authors: Petra
authors: P
authors: Steinacker
authors: Zenggang
authors: Z
authors: Li
authors: John
authors: J
authors: Yates
authors: Bruce
authors: B
authors: Herron
authors: Markus
authors: M
authors: Otto
authors: Hong
authors: H
authors: Zan
authors: Haian
authors: H
authors: Fu
authors: Paolo
authors: P
authors: Casali
mesh_terms: D048948:14-3-3 Proteins / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D003564:Cytidine Deaminase / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007134:Immunoglobulin Switch Region; D051379:Mice; D011485:Protein Binding; D011995:Recombination, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D048948:14-3-3 Proteins; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase