Abstract
The adipocyte-enhancer binding protein (AEBP) 1 is a novel transcriptional repressor with carboxypeptidase (CP) activity. AEBP1 binds to a regulatory sequence (termed adipocyte enhancer 1, AE-1) located in the proximal promoter region of the adipose P2 (aP2) gene, which encodes the adipocyte fatty-acid binding protein. Sequence comparisons and kinetic studies using known carboxypeptidase substrates, activators and inhibitors have characterized AEBP1 as a member of the regulatory B-like CP family. Significantly, the inherent CP activity of AEBP1 is stimulated by the AE-1 sequence. Our results indicate that AEBP1 is activated by a novel mechanism, wherby the direct binding of DNA enhances its protease activity. These results represent the first demonstration of DNA-mediated regulation of CP activity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites
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Carboxypeptidase B
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Carboxypeptidases / antagonists & inhibitors
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Carboxypeptidases / metabolism*
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Catalytic Domain
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DNA / metabolism*
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DNA / pharmacology
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DNA-Binding Proteins / agonists
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / metabolism
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Enhancer Elements, Genetic / genetics
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Enzyme Activation / drug effects
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Inhibitory Concentration 50
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Intercellular Signaling Peptides and Proteins
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Kinetics
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Membrane Proteins / agonists*
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Membrane Proteins / antagonists & inhibitors
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Membrane Proteins / metabolism*
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Promoter Regions, Genetic / genetics
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Repressor Proteins / agonists*
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Repressor Proteins / antagonists & inhibitors
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Repressor Proteins / metabolism*
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Substrate Specificity
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Zinc / metabolism
Substances
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DNA-Binding Proteins
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Intercellular Signaling Peptides and Proteins
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Membrane Proteins
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Recombinant Fusion Proteins
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Repressor Proteins
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DNA
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Carboxypeptidases
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Carboxypeptidase B
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Zinc