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Published on: August 9, 2019
Interaction between antibody-diversification enzyme AID and spliceosome-associated factor CTNNBL1
Silvestro G Conticello1, Karuna Ganesh1, Kanmin Xue1
1Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.
Molecular Cell
|August 30, 2008
Summary
Activation-induced deaminase (AID) interacts with CTNNBL1, a spliceosome component, to facilitate antibody diversification. This interaction is crucial for immunoglobulin gene hypermutation and class switching in B cells.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Activation-induced deaminase (AID) is essential for antibody diversification through deamination of deoxycytidine residues in immunoglobulin genes.
- The precise mechanisms regulating AID targeting and activity within B cells remain incompletely understood.
Purpose of the Study:
- To identify novel interactors of Activation-induced deaminase (AID).
- To elucidate the role of identified interactors in the processes of antibody diversification, including hypermutation and class switching.
Main Methods:
- Two-hybrid assays were employed to identify proteins interacting with AID.
- Coimmunoprecipitation assays were used to confirm the interaction between AID and CTNNBL1.
- Targeted inactivation of CTNNBL1 in DT40 B cells was performed to assess its functional role.
Main Results:
- CTNNBL1 (also known as NAP) was identified as an AID-specific interactor.
- Mutants of AID impairing CTNNBL1 interaction showed significantly reduced antibody hypermutation and class switching.
- Inactivation of CTNNBL1 in DT40 B cells led to a substantial decrease in immunoglobulin variable (IgV) diversification.
- CTNNBL1 was found to associate with the Prp19 complex of the spliceosome, specifically interacting with CDC5L.
Conclusions:
- CTNNBL1 is a key interactor of AID, essential for its function in antibody diversification.
- Specific residues in AID mediate interaction with CTNNBL1, influencing in vivo targeting.
- The interaction between AID and CTNNBL1 may link AID recruitment to target-gene transcription, offering insights into the regulation of antibody diversification.
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