title: REG-γ associates with and modulates the abundance of nuclear activation-induced deaminase.
abstract: Activation-induced deaminase (AID) acts on the immunoglobulin loci in activated B lymphocytes to initiate antibody gene diversification. The abundance of AID in the nucleus appears tightly regulated, with most nuclear AID being either degraded or exported back to the cytoplasm. To gain insight into the mechanisms regulating nuclear AID, we screened for proteins interacting specifically with it. We found that REG-γ, a protein implicated in ubiquitin- and ATP-independent protein degradation, interacts in high stoichiometry with overexpressed nuclear AID as well as with endogenous AID in B cells. REG-γ deficiency results in increased AID accumulation and increased immunoglobulin class switching. A stable stoichiometric AID-REG-γ complex can be recapitulated in co-transformed bacteria, and REG-γ accelerates proteasomal degradation of AID in in vitro assays. Thus, REG-γ interacts, likely directly, with nuclear AID and modulates the abundance of this antibody-diversifying but potentially oncogenic enzyme.
authors: Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
authors: Yasuhiro
authors: Y
authors: Uchimura
authors: Lance F
authors: LF
authors: Barton
authors: Cristina
authors: C
authors: Rada
authors: Michael S
authors: MS
authors: Neuberger
mesh_terms: D001324:Autoantigens / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D003564:Cytidine Deaminase / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000502:physiology; D047468:Immunoprecipitation; D013058:Mass Spectrometry; D008856:Microscopy, Fluorescence; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D001324:Autoantigens; C099558:Ki antigen; D046988:Proteasome Endopeptidase Complex; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase