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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
50
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pubmed:dateCreated |
2001-12-12
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pubmed:abstractText |
Accessibility of the genome to DNA-binding transcription factors is regulated by proteins that control the acetylation of amino-terminal lysine residues on nucleosomal histones. Specifically, histone deacetylase (HDAC) proteins repress transcription by deacetylating histones. To date, the only known regulatory mechanism of HDAC1 function is via interaction with associated proteins. Although the control of HDAC1 function by protein interaction and recruitment is well precedented, we were interested in exploring HDAC1 regulation by post-translational modification. Human HDAC1 protein was analyzed by ion trap mass spectrometry, and two phosphorylated serine residues, Ser(421) and Ser(423), were unambiguously identified. Loss of phosphorylation at Ser(421) and Ser(423) due to mutation to alanine or disruption of the casein kinase 2 consensus sequence directing phosphorylation reduced the enzymatic activity and complex formation of HDAC1. Deletion of the highly charged carboxyl-terminal region of HDAC1 also decreased its deacetylase activity and protein associations, revealing its requirement in maintaining HDAC1 function. Our results reinforce the importance of protein associations in modulating HDAC1 function and provide the first step toward characterizing the role of post-translational modifications in regulating HDAC activity in vivo.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Alanine,
http://linkedlifedata.com/resource/pubmed/chemical/Casein Kinase II,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/HDAC1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylases,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serine
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
14
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
47733-41
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11602581-Alanine,
pubmed-meshheading:11602581-Amino Acid Sequence,
pubmed-meshheading:11602581-Binding Sites,
pubmed-meshheading:11602581-Casein Kinase II,
pubmed-meshheading:11602581-Cell Division,
pubmed-meshheading:11602581-Gene Deletion,
pubmed-meshheading:11602581-Glutamic Acid,
pubmed-meshheading:11602581-Histone Deacetylase 1,
pubmed-meshheading:11602581-Histone Deacetylase 2,
pubmed-meshheading:11602581-Histone Deacetylases,
pubmed-meshheading:11602581-Humans,
pubmed-meshheading:11602581-Jurkat Cells,
pubmed-meshheading:11602581-Luciferases,
pubmed-meshheading:11602581-Mass Spectrometry,
pubmed-meshheading:11602581-Molecular Sequence Data,
pubmed-meshheading:11602581-Mutagenesis, Site-Directed,
pubmed-meshheading:11602581-Mutation,
pubmed-meshheading:11602581-Phosphorylation,
pubmed-meshheading:11602581-Plasmids,
pubmed-meshheading:11602581-Precipitin Tests,
pubmed-meshheading:11602581-Protein Binding,
pubmed-meshheading:11602581-Protein Processing, Post-Translational,
pubmed-meshheading:11602581-Protein Structure, Tertiary,
pubmed-meshheading:11602581-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11602581-Repressor Proteins,
pubmed-meshheading:11602581-Sequence Homology, Amino Acid,
pubmed-meshheading:11602581-Serine,
pubmed-meshheading:11602581-Transcription, Genetic,
pubmed-meshheading:11602581-Transfection
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pubmed:year |
2001
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pubmed:articleTitle |
Histone deacetylase 1 phosphorylation promotes enzymatic activity and complex formation.
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pubmed:affiliation |
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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