| Functional interplay between acetylation and methylation of the RelA subunit of NF-kappaB. | |
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MedLine Citation:
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PMID: 20160011 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Posttranslational modifications of the RelA subunit of NF-kappaB, including acetylation and methylation, play a key role in controlling the strength and duration of its nuclear activity. Whether these modifications are functionally linked is largely unknown. Here, we show that the acetylation of lysine 310 of RelA impairs the Set9-mediated methylation of lysines 314 and 315, which is important for the ubiquitination and degradation of chromatin-associated RelA. Abolishing the acetylation of lysine 310 either by the deacetylase SIRT1 or by mutating lysine 310 to arginine enhances methylation. Conversely, enhancing the acetylation of lysine 310 by depleting SIRT1 or by replacing lysine 310 with acetyl-mimetic glutamine inhibits methylation, thereby decreasing ubiquitination, prolonging the stability of chromatin-associated RelA, and enhancing the transcriptional activity of NF-kappaB. The acetylation of lysine 310 of RelA interferes with its interaction with Set9. Based on structural modeling of the SET domain of Set9 with RelA, we propose that the positive charge of lysine 310 is critical for the binding of RelA to a negatively charged "exosite" within the SET domain of Set9. Together, these findings demonstrate for the first time an interplay between RelA acetylation and methylation and also provide a novel mechanism for the regulation of lysine methylation by acetylation. |
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Authors:
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Xiao-Dong Yang; Emad Tajkhorshid; Lin-Feng Chen |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-02-16 |
Journal Detail:
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Title: Molecular and cellular biology Volume: 30 ISSN: 1098-5549 ISO Abbreviation: Mol. Cell. Biol. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-04-08 Completed Date: 2010-04-22 Revised Date: 2010-11-02 |
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: 2170-80 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, College of Medicine, MC-714, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetylation
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drug effects Amino Acid Sequence Animals Cell Line Glutamine / metabolism Histone-Lysine N-Methyltransferase / chemistry, metabolism Humans Lysine / metabolism Methylation / drug effects Mice Models, Biological Models, Molecular Molecular Sequence Data Mutation / genetics Promoter Regions, Genetic / genetics Protein Binding / drug effects Protein Stability / drug effects Protein Structure, Tertiary Protein Subunits / metabolism* Transcription Factor RelA / chemistry, metabolism* Tumor Necrosis Factor-alpha / pharmacology Ubiquitination / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Protein Subunits; 0/Transcription Factor RelA; 0/Tumor Necrosis Factor-alpha; 56-85-9/Glutamine; 56-87-1/Lysine; EC 2.1.1.43/Histone-Lysine N-Methyltransferase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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