title: AID mutant analyses indicate requirement for class-switch-specific cofactors.
abstract: Activation-induced cytidine deaminase (AID) is the essential and sole B cell-specific factor required for class-switch recombination (CSR) and somatic hypermutation (SHM). However, it is not known how AID differentially regulates these two independent events. Involvement of several cofactors interacting with AID has been indicated by scattered distribution of loss-of-function point mutations and evolutionary conservation of the entire 198-amino-acid protein. Here, we report that human AID mutant proteins with insertions, replacements or truncations in the C-terminal region retained strong SHM activity but almost completely lost CSR activity. These results indicate that AID requires interaction with a cofactor(s) specific to CSR.
authors.affiliation: Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo-ku, Kyoto, 606-8501, Japan.
authors.forename: Van-Thanh
authors.initials: VT
authors.lastname: Ta
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nagaoka
authors.forename: Nadia
authors.initials: N
authors.lastname: Catalan
authors.forename: Anne
authors.initials: A
authors.lastname: Durandy
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Imai
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Nonoyama
authors.forename: Junko
authors.initials: J
authors.lastname: Tashiro
authors.forename: Masaya
authors.initials: M
authors.lastname: Ikegawa
authors.forename: Satomi
authors.initials: S
authors.lastname: Ito
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kinoshita
authors.forename: Masamichi
authors.initials: M
authors.lastname: Muramatsu
authors.forename: Tasuku
authors.initials: T
authors.lastname: Honjo
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D003564:Cytidine Deaminase / Q000235:genetics / Q000276:immunology*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D007105:Immune Complex Diseases / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000235:genetics / Q000276:immunology*; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology; D007134:Immunoglobulin Switch Region / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000276:immunology; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics / Q000276:immunology*; D014162:Transfection
chemical_list: D007075:Immunoglobulin M; D011994:Recombinant Proteins; D004247:DNA; D003564:Cytidine Deaminase