Document Detail


Interaction between antibody-diversification enzyme AID and spliceosome-associated factor CTNNBL1.
MedLine Citation:
PMID:  18722174     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Silvestro G Conticello; Karuna Ganesh; Kanmin Xue; Mason Lu; Cristina Rada; Michael S Neuberger
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Molecular cell     Volume:  31     ISSN:  1097-4164     ISO Abbreviation:  Mol. Cell     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-08-25     Completed Date:  2008-09-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9802571     Medline TA:  Mol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  474-84     Citation Subset:  IM    
Affiliation:
Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB20QH, UK. silvo.conticello@ittumori.it
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibody Diversity*
Apoptosis Regulatory Proteins / metabolism*
Cell Cycle Proteins / metabolism
Cell Line
Cell Nucleus / metabolism
Chickens
Cytidine Deaminase / metabolism*
Humans
Mutant Proteins / metabolism
Mutation / genetics
Nuclear Proteins / metabolism*
Protein Binding
RNA-Binding Proteins / metabolism
Rats
Spliceosomes / metabolism*
Two-Hybrid System Techniques
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/CDC5L protein, human; 0/CTNNBL1 protein, human; 0/Cell Cycle Proteins; 0/Mutant Proteins; 0/Nuclear Proteins; 0/RNA-Binding Proteins; EC 3.5.4.-/AICDA (activation-induced cytidine deaminase); EC 3.5.4.5/Cytidine Deaminase
Comments/Corrections
Comment In:
Mol Cell. 2008 Sep 5;31(5):615-6   [PMID:  18775319 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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