Interaction between anti body-diversification enzyme AID and spliceosome-associated factor CTNNBL1

被引:109
作者
Conticello, Silvestro G. [1 ]
Ganesh, Karuna [1 ]
Xue, Kanmin [1 ]
Lu, Mason [1 ]
Rada, Cristina [1 ]
Neuberger, Michael S. [1 ]
机构
[1] MRC, Mol Biol Lab, Cambridge CB2 0QH, England
基金
英国医学研究理事会;
关键词
D O I
10.1016/j.molcel.2008.07.009
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Activation-induced deaminase (AID) deaminates deoxycytidine residues in immunoglobulin genes, triggering antibody diversification. Here, by use of two-hybrid and coimmunoprecipitation assays, we identify CTNNBL1 (also known as NAP) as an AID-specific interactor. Mutants of AID that interfere with CTNNBL1 interaction yield severely diminished hypermutation and class switching. Targeted inactivation of CTNNBL1 in DT40 B cells also considerably diminishes IgV diversification. CTNNBL1 is a widely expressed nuclear protein that associates with the Prp19 complex of the spliceosome, interacting with its CDC5L component. The results, therefore, identify residues in AID involved in its in vivo targeting and suggest they might act through interaction with CTNNBL1, giving possible insight into the linkage between AID recruitment and target-gene transcription.
引用
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页码:474 / 484
页数:11
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