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 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.
Stein
Susanne
S
Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA. S.Stein@med.uni-frankfurt.de
Thomas
Emily K
EK
Herzog
Birger
B
Westfall
Matthew D
MD
Rocheleau
Jonathan V
JV
Jackson
Roger S
RS
Wang
Mai
M
Liang
Peng
P
D000595:Amino Acid Sequence; D017209:Apoptosis; D001483:Base Sequence; D001665:Binding Sites; D015152:Blotting, Northern; D002118:Calcium / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D047369:Chromatin Immunoprecipitation; D004249:DNA Damage; D015536:Down-Regulation; D004789:Enzyme Activation; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013050:Spectrometry, Fluorescence; D013752:Tetracycline / Q000494:pharmacology; D013997:Time Factors; D015533:Transcriptional Activation; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation; D000099259:N-myc Downstream-Regulated Gene 1 Protein
D002118:Calcium; D020169:Caspases; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D013752:Tetracycline; D016159:Tumor Suppressor Protein p53; D000099259:N-myc Downstream-Regulated Gene 1 Protein