Abstract
The transcription of p53 target genes involves p300/CBP coactivators, which are multiprotein complexes that interact with the p53 activation domain. We report a cofactor in the p300 coactivator complex, Strap, which has an unusual structure, being composed almost entirely of a tandem series of six tetratricopeptide repeat (TPR) motifs. The TPR motif functions as a protein interaction domain, and it is consistent with this property that Strap harbors distinct and dedicated domains that allow it to bind and augment the interaction between different components of the p300 complex. Strap facilitates p53 activity in response to stress, in part through the stress-responsive accumulation of Strap protein and interfering with the MDM2-dependent downregulation of p53.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetyltransferases / genetics
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Acetyltransferases / metabolism*
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Amino Acid Motifs*
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Amino Acid Sequence
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Apoptosis / physiology
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Cell Line
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Etoposide / pharmacology
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Gene Expression Regulation*
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Genes, Reporter
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Histone Acetyltransferases
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Humans
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Immunoblotting
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Macromolecular Substances
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Molecular Sequence Data
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Multiprotein Complexes
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Nucleic Acid Synthesis Inhibitors / pharmacology
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Precipitin Tests
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Protein Binding
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Protein Structure, Tertiary
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-mdm2
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Radiation, Ionizing
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Serine Endopeptidases
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Stress, Physiological
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Transcription Factors
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Transfection
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism*
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Two-Hybrid System Techniques
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Ultraviolet Rays
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p300-CBP Transcription Factors
Substances
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Carrier Proteins
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Cell Cycle Proteins
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JMY protein, human
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Macromolecular Substances
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Multiprotein Complexes
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Nuclear Proteins
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Nucleic Acid Synthesis Inhibitors
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Proto-Oncogene Proteins
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Strap protein
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Trans-Activators
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Transcription Factors
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Tumor Suppressor Protein p53
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Etoposide
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Acetyltransferases
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Histone Acetyltransferases
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p300-CBP Transcription Factors
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p300-CBP-associated factor
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MDM2 protein, human
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Proto-Oncogene Proteins c-mdm2
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SRAP protein, Luidia foliolata
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Serine Endopeptidases