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Proteasomal degradation restricts the nuclear lifespan of AID
Activation-induced cytidine deaminase (AID) initiates all postrearrangement processes that diversify the immunoglobulin repertoire by specific deamination of cytidines at the immunoglobulin (Ig) locus. As uncontrolled expression of AID is potentially mutagenic, different types of regulation, particu...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2413033/ https://www.ncbi.nlm.nih.gov/pubmed/18474627 http://dx.doi.org/10.1084/jem.20070950 |
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author | Aoufouchi, Said Faili, Ahmad Zober, Carole D'Orlando, Orietta Weller, Sandra Weill, Jean-Claude Reynaud, Claude-Agnès |
author_facet | Aoufouchi, Said Faili, Ahmad Zober, Carole D'Orlando, Orietta Weller, Sandra Weill, Jean-Claude Reynaud, Claude-Agnès |
author_sort | Aoufouchi, Said |
collection | PubMed |
description | Activation-induced cytidine deaminase (AID) initiates all postrearrangement processes that diversify the immunoglobulin repertoire by specific deamination of cytidines at the immunoglobulin (Ig) locus. As uncontrolled expression of AID is potentially mutagenic, different types of regulation, particularly nucleocytoplasmic shuttling, restrict the likelihood of AID–deoxyribonucleic acid encounters. We studied additional mechanisms of regulation affecting the stability of the AID protein. No modulation of protein accumulation according to the cell cycle was observed in a Burkitt's lymphoma cell line. In contrast, the half-life of AID was markedly reduced in the nucleus, and this destabilization was accompanied by a polyubiquitination that was revealed in the presence of proteasome inhibitors. The same compartment-specific degradation was observed in activated mouse B cells, and also in a non–B cell line. No specific lysine residues could be linked to this degradation, so it remains unclear whether polyubiquitination proceeds through several alternatives sites or through the protein N terminus. The nuclear-restricted form of AID displayed enhanced mutagenicity at both Ig and non-Ig loci, most notably at TP53, suggesting that modulation of nuclear AID content through proteasomal degradation may represent another level of control of AID activity. |
format | Text |
id | pubmed-2413033 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-24130332008-12-09 Proteasomal degradation restricts the nuclear lifespan of AID Aoufouchi, Said Faili, Ahmad Zober, Carole D'Orlando, Orietta Weller, Sandra Weill, Jean-Claude Reynaud, Claude-Agnès J Exp Med Articles Activation-induced cytidine deaminase (AID) initiates all postrearrangement processes that diversify the immunoglobulin repertoire by specific deamination of cytidines at the immunoglobulin (Ig) locus. As uncontrolled expression of AID is potentially mutagenic, different types of regulation, particularly nucleocytoplasmic shuttling, restrict the likelihood of AID–deoxyribonucleic acid encounters. We studied additional mechanisms of regulation affecting the stability of the AID protein. No modulation of protein accumulation according to the cell cycle was observed in a Burkitt's lymphoma cell line. In contrast, the half-life of AID was markedly reduced in the nucleus, and this destabilization was accompanied by a polyubiquitination that was revealed in the presence of proteasome inhibitors. The same compartment-specific degradation was observed in activated mouse B cells, and also in a non–B cell line. No specific lysine residues could be linked to this degradation, so it remains unclear whether polyubiquitination proceeds through several alternatives sites or through the protein N terminus. The nuclear-restricted form of AID displayed enhanced mutagenicity at both Ig and non-Ig loci, most notably at TP53, suggesting that modulation of nuclear AID content through proteasomal degradation may represent another level of control of AID activity. The Rockefeller University Press 2008-06-09 /pmc/articles/PMC2413033/ /pubmed/18474627 http://dx.doi.org/10.1084/jem.20070950 Text en © 2008 Aoufouchi et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jgp.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Articles Aoufouchi, Said Faili, Ahmad Zober, Carole D'Orlando, Orietta Weller, Sandra Weill, Jean-Claude Reynaud, Claude-Agnès Proteasomal degradation restricts the nuclear lifespan of AID |
title | Proteasomal degradation restricts the nuclear lifespan of AID |
title_full | Proteasomal degradation restricts the nuclear lifespan of AID |
title_fullStr | Proteasomal degradation restricts the nuclear lifespan of AID |
title_full_unstemmed | Proteasomal degradation restricts the nuclear lifespan of AID |
title_short | Proteasomal degradation restricts the nuclear lifespan of AID |
title_sort | proteasomal degradation restricts the nuclear lifespan of aid |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2413033/ https://www.ncbi.nlm.nih.gov/pubmed/18474627 http://dx.doi.org/10.1084/jem.20070950 |
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