NDRG1 Is Necessary for p53-dependent Apoptosis

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...

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Bibliographic Details
Published in:The Journal of biological chemistry 2004-11, Vol.279 (47), p.48930-48940
Main Authors: Stein, Susanne, Thomas, Emily K, Herzog, Birger, Westfall, Matthew D, Rocheleau, Jonathan V, Jackson, 2nd, Roger S, Wang, Mai, Liang, Peng
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Apoptosis
Base Sequence
Binding Sites
Blotting, Northern
Calcium - metabolism
Caspases - metabolism
Cell Cycle Proteins - genetics
Cell Cycle Proteins - physiology
Cell Line, Tumor
Cell Proliferation
Cell Separation
Chromatin Immunoprecipitation
DNA Damage
Down-Regulation
Enzyme Activation
Flow Cytometry
Gene Expression Profiling
Genes, Reporter
Humans
Intracellular Signaling Peptides and Proteins
Molecular Sequence Data
Plasmids - metabolism
Point Mutation
Promoter Regions, Genetic
Protein Binding
Reverse Transcriptase Polymerase Chain Reaction
RNA Interference
RNA, Messenger - metabolism
RNA, Small Interfering - metabolism
Spectrometry, Fluorescence
Tetracycline - pharmacology
Time Factors
Transcriptional Activation
Transfection
Tumor Suppressor Protein p53 - metabolism
Up-Regulation
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Summary: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 d own- r egulated g ene 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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M400386200