期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 17, 期 9, 页码 1124-U13出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.1884
关键词
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资金
- US National Institutes of Health (NIH) [P01 CA 116676]
- NIH [P41 RR011823, AI 045011, AI 079705, AI 060573]
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 mu -> S gamma 1, S mu -> S gamma 3 or S mu -> S alpha). Moreover, blocking 14-3-3 by difopein, 14-3-3 gamma deficiency or expression of a dominant-negative 14-3-3 sigma 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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