Abstract
Phosphorylation of the estrogen receptor alpha (ERalpha) N-terminal transcription activation function AF1 at serine 118 (S118) modulates its activity. We show here that human ERalpha is phosphorylated by the TFIIH cyclin-dependent kinase in a ligand-dependent manner. Furthermore, the efficient phosphorylation of S118 requires a ligand-regulated interaction of TFIIH with AF2, the activation function located in the ligand binding domain (LBD) of ERalpha. This interaction involves (1) the integrity of helix 12 of the LBD/AF2 and (2) p62 and XPD, two subunits of the core TFIIH. These findings are suggestive of a novel mechanism by which nuclear receptor activity can be regulated by ligand-dependent recruitment of modifying activities, such as kinases.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs
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Amino Acid Sequence
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Animals
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Binding Sites
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COS Cells
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Cyclin-Dependent Kinase-Activating Kinase
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Cyclin-Dependent Kinases*
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Estrogen Receptor alpha
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Humans
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In Vitro Techniques
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Ligands
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Molecular Sequence Data
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Phosphorylation
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Protein Serine-Threonine Kinases / metabolism*
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Protein Structure, Quaternary
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Protein Structure, Tertiary
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Receptors, Estrogen / chemistry
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Receptors, Estrogen / genetics
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Receptors, Estrogen / metabolism*
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Serine / metabolism
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Transcription Factor TFIIH
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcription Factors, TFII*
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Transcriptional Activation
Substances
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Estrogen Receptor alpha
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Ligands
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Receptors, Estrogen
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Recombinant Proteins
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Transcription Factors
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Transcription Factors, TFII
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Transcription Factor TFIIH
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Serine
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Protein Serine-Threonine Kinases
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Cyclin-Dependent Kinases
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Cyclin-Dependent Kinase-Activating Kinase
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CDK7 protein, human