Abstract
PA28γ (also called REGγ, 11Sγ or PSME3) negatively regulates p53 activity by promoting its nuclear export and/or degradation. Here, using the RNA ligase-mediated rapid amplification of cDNA ends (RLM-RACE) method, we identified the transcription start site of the PA28γ gene. Assessment with the luciferase assay demonstrated that the sequence -193 to +16 is the basal promoter. Three p53 binding sites were found within the PA28γ promoter utilizing a bioinformatics approach and were confirmed by chromatin immunoprecipitation and biotinylated DNA affinity precipitation experiments. The p53 protein promotes PA28γ transcription, and p53-stimulated transcription of PA28γ can be inhibited by PA28γ itself. Our results suggest that PA28γ and p53 form a negative feedback loop, which maintains the balance of p53 and PA28γ in cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Autoantigens / genetics
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Autoantigens / metabolism*
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HEK293 Cells
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Humans
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Promoter Regions, Genetic
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Proteasome Endopeptidase Complex / genetics
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Proteasome Endopeptidase Complex / metabolism*
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Protein Binding
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RNA Interference
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RNA, Messenger / metabolism
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RNA, Small Interfering / metabolism
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / genetics
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Recombinant Proteins / pharmacology
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Response Elements / genetics
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Transcription, Genetic
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Tumor Suppressor Protein p53 / antagonists & inhibitors
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism*
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Up-Regulation / drug effects
Substances
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Autoantigens
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Ki antigen
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RNA, Messenger
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RNA, Small Interfering
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Recombinant Proteins
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Tumor Suppressor Protein p53
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Proteasome Endopeptidase Complex