| Amino-terminal phosphorylation of activation-induced cytidine deaminase suppresses c-myc/IgH translocation. | |
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MedLine Citation:
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PMID: 21135131 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Activation-induced cytidine deaminase (AID) is a mutator enzyme that initiates class switch recombination and somatic hypermutation of immunoglobulin genes (Ig) in B lymphocytes. However, AID also produces off-target DNA damage, including mutations in oncogenes and double-stranded breaks that can serve as substrates for oncogenic chromosomal translocations. AID is strictly regulated by a number of mechanisms, including phosphorylation at serine 38 and threonine 140, which increase activity. Here we show that phosphorylation can also suppress AID activity in vivo. Serine 3 is a novel phospho-acceptor which, when mutated to alanine, leads to increased class switching and c-myc/IgH translocations without affecting AID levels or catalytic activity. Conversely, increasing AID phosphorylation specifically on serine 3 by interfering with serine/threonine protein phosphatase 2A (PP2A) leads to decreased class switching. We conclude that AID activity and its oncogenic potential can be downregulated by phosphorylation of serine 3 and that this process is controlled by PP2A. |
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Authors:
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Anna Gazumyan; Ksenia Timachova; Grace Yuen; Edward Siden; Michela Di Virgilio; Eileen M Woo; Brian T Chait; Bernardo Reina San-Martin; Michel C Nussenzweig; Kevin M McBride |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-12-06 |
Journal Detail:
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Title: Molecular and cellular biology Volume: 31 ISSN: 1098-5549 ISO Abbreviation: Mol. Cell. Biol. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-17 Completed Date: 2011-02-24 Revised Date: 2011-08-03 |
Medline Journal Info:
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Nlm Unique ID: 8109087 Medline TA: Mol Cell Biol Country: United States |
Other Details:
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Languages: eng Pagination: 442-9 Citation Subset: IM |
Affiliation:
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Laboratory of Molecular Immunology, Rockefeller University, 1230 York Ave., New York, NY 10065, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Amino Acid Substitution / genetics Animals Cytidine Deaminase / chemistry*, metabolism* Enzyme Inhibitors / pharmacology Fibroblasts / drug effects, enzymology Immunoglobulin Class Switching / drug effects Immunoglobulin Heavy Chains / genetics* Mice Molecular Sequence Data Mutant Proteins / metabolism Phosphorylation / drug effects Phosphoserine / metabolism Protein Phosphatase 2 / antagonists & inhibitors, metabolism Proto-Oncogene Proteins c-myc / genetics* Recombination, Genetic / drug effects, genetics Somatic Hypermutation, Immunoglobulin / drug effects, genetics Translocation, Genetic* / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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R01AI03752616/AI/NIAID NIH HHS; RR00862/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Immunoglobulin Heavy Chains; 0/Mutant Proteins; 0/Proto-Oncogene Proteins c-myc; 17885-08-4/Phosphoserine; EC 3.1.3.16/Protein Phosphatase 2; EC 3.5.4.-/AICDA (activation-induced cytidine deaminase); EC 3.5.4.5/Cytidine Deaminase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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