NDRG1 is necessary for p53-dependent apoptosis

J Biol Chem. 2004 Nov 19;279(47):48930-40. doi: 10.1074/jbc.M400386200. Epub 2004 Sep 17.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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
  • RNA Interference
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spectrometry, Fluorescence
  • Tetracycline / pharmacology
  • Time Factors
  • Transcriptional Activation
  • Transfection
  • Tumor Suppressor Protein p53 / metabolism*
  • Up-Regulation

Substances

  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • N-myc downstream-regulated gene 1 protein
  • RNA, Messenger
  • RNA, Small Interfering
  • Tumor Suppressor Protein p53
  • Caspases
  • Tetracycline
  • Calcium