Abstract
Although a number of target genes for the tumor suppressor p53 have been described, the mechanism of p53-dependent apoptosis is incompletely understood. Thus, it is essential to identify and characterize additional target genes that could mediate apoptosis. In the study reported here, we isolated a p53-regulated gene named NDRG1 (N-Myc down-regulated gene 1). Its expression is induced by DNA damage in a p53-dependent fashion. The promoter region of the NDRG1 gene contains a p53 binding site that confers p53-dependent transcriptional activation via a heterologous reporter. RNA interference and inducible gene expression approaches suggest that NDRG1 is necessary but not sufficient for p53-mediated caspase activation and apoptosis. This report further supports the notion that p53 controls a network of genes that are required for its apoptotic function.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Apoptosis*
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Base Sequence
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Binding Sites
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Blotting, Northern
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Calcium / metabolism
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Caspases / metabolism
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / physiology*
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Cell Line, Tumor
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Cell Proliferation
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Cell Separation
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Chromatin Immunoprecipitation
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DNA Damage
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Down-Regulation
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Enzyme Activation
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Flow Cytometry
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Gene Expression Profiling
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Genes, Reporter
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Humans
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Intracellular Signaling Peptides and Proteins
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Molecular Sequence Data
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Plasmids / metabolism
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Point Mutation
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Promoter Regions, Genetic
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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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Reverse Transcriptase Polymerase Chain Reaction
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Spectrometry, Fluorescence
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Tetracycline / pharmacology
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Time Factors
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Transcriptional Activation
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Transfection
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Tumor Suppressor Protein p53 / metabolism*
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Up-Regulation
Substances
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Cell Cycle Proteins
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Intracellular Signaling Peptides and Proteins
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N-myc downstream-regulated gene 1 protein
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RNA, Messenger
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RNA, Small Interfering
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Tumor Suppressor Protein p53
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Caspases
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Tetracycline
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Calcium