Abstract
Steroidogenic factor 1 (SF-1) is a nuclear receptor essential for steroidogenic gene expression, but how its activity is regulated is unclear. Here we demonstrate that p300 plays an important role in regulating SF-1 function. SF-1 was acetylated in vitro and in vivo by p300 at the KQQKK motif in the Ftz-F1 (Fushi-tarazu factor 1) box adjacent to its DNA-binding domain. Mutation of the KQQKK motif reduced the DNA-binding activity and p300-dependent activation of SF-1. When stimulated with cyclic AMP (cAMP), adrenocortical Y1 cells expressed more p300, leading to additional SF-1 association with p300 and increased SF-1 acetylation and DNA binding. It also increased SF-1 colocalization with p300 in nuclear foci. Collectively, these results indicate that SF-1 transcriptional activity is regulated by p300 in response to the cAMP signaling pathway by way of increased acetylation, DNA binding, and recruitment to nuclear foci.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation
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Amino Acid Sequence
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Animals
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Cell Line
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Cell Nucleus / genetics
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Cell Nucleus / metabolism
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Cyclic AMP / metabolism*
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DNA / metabolism*
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Homeodomain Proteins / chemistry
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism*
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Humans
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Mice
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Molecular Sequence Data
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Mutation / genetics
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Protein Binding
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Protein Transport
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Receptors, Cytoplasmic and Nuclear / chemistry
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Sequence Alignment
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Sequence Homology, Amino Acid
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Steroidogenic Factor 1
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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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p300-CBP Transcription Factors / genetics
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p300-CBP Transcription Factors / metabolism*
Substances
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Homeodomain Proteins
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NR5A1 protein, human
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Receptors, Cytoplasmic and Nuclear
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Steroidogenic Factor 1
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Transcription Factors
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steroidogenic factor 1, mouse
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DNA
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Cyclic AMP
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p300-CBP Transcription Factors