Abstract
GDF15 is a transcriptional target gene for p53 and its family members, p63 and p73. Its promoter region contains two p53-type response elements, RE1 and RE2, and RE2 confers p53-specific transactivation. RE2 contains several mismatches from the canonical p53 response element (RRRCWWGYYY). Two mismatches in the RRR span and T base of the RE2 core sequence in the most 3' quarter-site are critical for inhibiting the binding affinity to p63 and p73 and corresponding promoter activity. Our results strongly suggest that differential DNA-binding affinities between p53 family member proteins act, at least in part, to confer specific target gene activation.
MeSH terms
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Amino Acid Sequence
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Base Sequence
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Bone Morphogenetic Proteins / genetics*
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Cell Line, Tumor
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DNA-Binding Proteins / metabolism
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Growth Differentiation Factor 15
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Humans
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Nuclear Proteins / metabolism
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Osteosarcoma / metabolism
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Promoter Regions, Genetic / physiology*
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Response Elements / genetics
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Response Elements / physiology*
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Trans-Activators / metabolism
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Transcription Factors
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Transcriptional Activation
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Tumor Protein p73
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Tumor Suppressor Protein p53 / genetics*
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Tumor Suppressor Protein p53 / physiology*
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Tumor Suppressor Proteins / metabolism
Substances
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Bone Morphogenetic Proteins
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DNA-Binding Proteins
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GDF15 protein, human
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Growth Differentiation Factor 15
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Nuclear Proteins
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TP63 protein, human
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TP73 protein, human
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Trans-Activators
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Transcription Factors
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Tumor Protein p73
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Tumor Suppressor Protein p53
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Tumor Suppressor Proteins