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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2008-3-26
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pubmed:abstractText |
Class IIa histone deacetylases (HDACs) act as key transcriptional regulators in several important developmental programs. Their activities are controlled via phosphorylation-dependent nucleocytoplasmic shuttling. Phosphorylation of conserved serine residues triggers association with 14-3-3 proteins and cytoplasmic relocalization of class IIa HDACs, which leads to the derepression of their target genes. Although a lot of effort has been made toward the identification of the inactivating kinases that phosphorylate class IIa HDAC 14-3-3 motifs, the existence of an antagonistic protein phosphatase remains elusive. Here we identify PP2A as a phosphatase responsible for dephosphorylating the 14-3-3 binding sites in class IIa HDACs. Interestingly, dephosphorylation of class IIa HDACs by PP2A is prevented by competitive association of 14-3-3 proteins. Using both okadaic acid treatment and RNA interference, we demonstrate that PP2A constitutively dephosphorylates the class IIa member HDAC7 to control its biological functions as a regulator of T cell apoptosis and endothelial cell functions. This study unravels a dynamic interplay among 14-3-3s, protein kinases, and PP2A and provides a model for the regulation of class IIa HDACs.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-10485875,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-10493820,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-11081517,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-11114197,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-11292821,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-11585834,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-11779871,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-11804585,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-11978735,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-12202037,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-12369865,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-12641737,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-12663674,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-12753745,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-12896970,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-15124925,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-15367668,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-15537544,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-15711539,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-15738054,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-15923258,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-16038801,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-16100571,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-16449666,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-16873063,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-16980613,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-17369396,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-17694086,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-9428519,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18339811-9712047
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1091-6490
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
25
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pubmed:volume |
105
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4727-32
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pubmed:dateRevised |
2009-12-11
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pubmed:meshHeading |
pubmed-meshheading:18339811-14-3-3 Proteins,
pubmed-meshheading:18339811-Apoptosis,
pubmed-meshheading:18339811-Cell Line,
pubmed-meshheading:18339811-Cytoplasm,
pubmed-meshheading:18339811-Enzyme Inhibitors,
pubmed-meshheading:18339811-Histone Deacetylases,
pubmed-meshheading:18339811-Humans,
pubmed-meshheading:18339811-Neovascularization, Physiologic,
pubmed-meshheading:18339811-Phosphorylation,
pubmed-meshheading:18339811-Protein Binding,
pubmed-meshheading:18339811-Protein Phosphatase 2,
pubmed-meshheading:18339811-Protein Transport,
pubmed-meshheading:18339811-RNA, Small Interfering,
pubmed-meshheading:18339811-Repressor Proteins,
pubmed-meshheading:18339811-Subcellular Fractions,
pubmed-meshheading:18339811-T-Lymphocytes
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pubmed:year |
2008
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pubmed:articleTitle |
Protein phosphatase 2A controls the activity of histone deacetylase 7 during T cell apoptosis and angiogenesis.
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pubmed:affiliation |
Cellular and Molecular Biology Unit, FUSAGx, 5030 Gembloux, Belgium.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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