REG-γ, a protein involved in protein degradation, binds to nuclear AID, and REG-γ–deficient B cells contain more AID and exhibit increased immunoglobulin class switching

Aoufouchi

Barton

Brar

Bürckstümmer

Chen

Cristina Rada

de Yébenes

Dorsett

Geisberger

Jankovic

Lance F. Barton

Maul

McBride

Michael S. Neuberger

Murata

Pérez-Durán

Rechsteiner

Sernández

Sijts

Stavnezer

Teng

Yamane

Yasuhiro Uchimura

Yasukawa

Zhang

Zhou

English

PubMed

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.</jats:p

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http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3256965

REG-γ associates with and modulates the abundance of nuclear activation-induced deaminase

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