Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 2096K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Aoufouchi, S. Articles by Reynaud, C.-A. Search for Related Content PubMed PubMed Citation Articles by Aoufouchi, S. Articles by Reynaud, C.-A. Social Bookmarking                      What's this?

¹ Institut National de la Santé et de la Recherche Médicale U783, Développement du Système Immunitaire, and Université Paris Descartes, Faculté de Médecine, Site Necker-Enfants Malades, 75730 Paris Cedex 15, France
² Dipartimento di Scienze e Tecnologie Biomediche, M.A.T.I. Center of Excellence, Universita degli Studi di Udine, 33100 Udine, Italy

CORRESPONDENCE Claude-Agnès Reynaud: reynaud{at}necker.fr OR Jean-Claude Weill: weill{at}necker.fr

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.

© 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/).

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Pauklin, S., Burkert, J. S., Martin, J., Osman, F., Weller, S., Boulton, S. J., Whitby, M. C., Petersen-Mahrt, S. K. (2009). Alternative Induction of Meiotic Recombination From Single-Base Lesions of DNA Deaminases. Genetics 182: 41-54 [Abstract] [Full Text]  
• Geisberger, R., Rada, C., Neuberger, M. S. (2009). The stability of AID and its function in class-switching are critically sensitive to the identity of its nuclear-export sequence. Proc. Natl. Acad. Sci. USA 106: 6736-6741 [Abstract] [Full Text]  
• Reynaud, C.-A., Delbos, F., Faili, A., Gueranger, Q., Aoufouchi, S., Weill, J.-C. (2009). Competitive repair pathways in immunoglobulin gene hypermutation. Phil Trans R Soc B 364: 613-619 [Abstract] [Full Text]  
• Basu, U., Franklin, A., Alt, F. W (2009). Post-translational regulation of activation-induced cytidine deaminase. Phil Trans R Soc B 364: 667-673 [Abstract] [Full Text]  
• Cheng, H.-L., Vuong, B. Q., Basu, U., Franklin, A., Schwer, B., Astarita, J., Phan, R. T., Datta, A., Manis, J., Alt, F. W., Chaudhuri, J. (2009). Integrity of the AID serine-38 phosphorylation site is critical for class switch recombination and somatic hypermutation in mice. Proc. Natl. Acad. Sci. USA 106: 2717-2722 [Abstract] [Full Text]  
• Maul, R. W., Gearhart, P. J. (2009). Women, autoimmunity, and cancer: a dangerous liaison between estrogen and activation-induced deaminase?. JEM 206: 11-13 [Abstract] [Full Text]  
• McBride, K. M., Gazumyan, A., Woo, E. M., Schwickert, T. A., Chait, B. T., Nussenzweig, M. C. (2008). Regulation of class switch recombination and somatic mutation by AID phosphorylation. JEM 205: 2585-2594 [Abstract] [Full Text]  
• Aoufouchi, S., Faili, A., Zober, C., D'Orlando, O., Weller, S., Weill, J.-C., Reynaud, C.-A. (2008). Proteasomal degradation restricts the nuclear lifespan of AID. JCB 181: i15-i15 [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS