Abstract
CtBP corepressor proteins potentiate the activity of many metazoan transcriptional repressors. These proteins are homologous to prokaryotic D-2-hydroxyacid dehydrogenases, possessing an NAD/NADH binding fold and conserved active site residues. When expressed in Drosophila, a catalytic site mutant retains biological activity, however, we find that an NAD binding mutant lacks biological activity. The NAD mutant, similar to a dimerization mutant, is expressed at low levels, indicating that binding of NAD/NADH may affect CtBP stability. These data support the idea that the ancestral dehydrogenase activity is not required for CtBP function, and NAD binding may play a regulatory, rather than catalytic, role.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Alcohol Oxidoreductases / chemistry*
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Alcohol Oxidoreductases / genetics
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Alcohol Oxidoreductases / metabolism*
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Animals
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Animals, Genetically Modified
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Base Sequence
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Binding Sites / genetics
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DNA, Complementary / genetics
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Drosophila / embryology
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Drosophila / genetics
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Drosophila / metabolism
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Drosophila Proteins / chemistry
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism
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Mutation
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NAD / metabolism*
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Phenotype
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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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Repressor Proteins / chemistry
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
Substances
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DNA, Complementary
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DNA-Binding Proteins
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Drosophila Proteins
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Recombinant Proteins
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Repressor Proteins
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NAD
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Alcohol Oxidoreductases
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C-terminal binding protein