The interaction between AID and CIB1 is nonessential for antibody gene diversification by gene conversion or class switch recombination.

PloS One
Zachary L DemorestReuben S Harris

Abstract

Activation-induced deaminase (AID) initiates somatic hypermutation, gene conversion and class switch recombination by deaminating variable and switch region DNA cytidines to uridines. AID is predominantly cytoplasmic and must enter the nuclear compartment to initiate these distinct antibody gene diversification reactions. Nuclear AID is relatively short-lived, as it is efficiently exported by a CRM1-dependent mechanism and it is susceptible to proteasome-dependent degradation. To help shed light on mechanisms of post-translational regulation, a yeast-based screen was performed to identify AID-interacting proteins. The calcium and integrin binding protein CIB1 was identified by sequencing and the interaction was confirmed by immunoprecipitation experiments. The AID/CIB1 resisted DNase and RNase treatment, and it is therefore unlikely to be mediated by nucleic acid. The requirement for CIB1 in AID-mediated antibody gene diversification reactions was assessed in CIB1-deficient DT40 cells and in knockout mice, but immunoglobulin gene conversion and class switch recombination appeared normal. The DT40 system was also used to show that CIB1 over-expression has no effect on gene conversion and that AID-EGFP subcellular localization is...Continue Reading

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Citations

Nov 28, 2012·Autoimmunity·Hong Zan, Paolo Casali
Jun 16, 2012·Seminars in Immunology·Julien HäslerMichael S Neuberger
Jun 15, 2012·Seminars in Immunology·Mani Larijani, Alberto Martin
Feb 1, 2012·Molecular and Cellular Biology·Kristina Zaprazna, Michael L Atchison
Apr 28, 2016·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Tina M LeisnerLeslie V Parise

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Methods Mentioned

BETA
ubiquitination
two-hybrid
co-immunoprecipitation
co-IP
co-IPs
pulls down
pull-down
tandem affinity purification
flow cytometry
PCR

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