N-Myc downstream-regulated gene 2 is involved in p53-mediated apoptosis

Na Liu1, Lifeng Wang, Xia Li

  • 1Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, Biotechnology Center, Department of Immunology, The Fourth Military Medical University, Xi'an, 710032, China.

Nucleic Acids Research
|August 12, 2008
PubMed

Insights

The tumor suppressor p53 regulates N-Myc downstream-regulated gene 2 (NDRG2), a novel target involved in apoptosis. NDRG2 influences p53-mediated apoptosis and tumor cell growth.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Genetics

Background:

  • The tumor suppressor p53 is a transcription factor crucial for regulating genes involved in cell-cycle arrest and apoptosis.
  • The precise mechanisms of p53-mediated apoptosis are not fully elucidated.

Purpose of the Study:

  • To identify novel target genes regulated by p53.
  • To investigate the role of N-Myc downstream-regulated gene 2 (NDRG2) in p53-mediated apoptosis.

Main Methods:

  • Investigated NDRG2 gene regulation by p53 using mRNA and protein level analysis.
  • Identified a p53 binding site within the first intron of the NDRG2 gene.
  • Assessed the impact of NDRG2 silencing and overexpression on p53-mediated apoptosis and tumor cell growth.

Main Results:

  • NDRG2 mRNA and protein levels are upregulated in a p53-dependent manner.
  • A direct binding site for p53 was identified in the NDRG2 gene's first intron, mediating transactivation.
  • Silencing NDRG2 reduced p53-induced apoptosis, while NDRG2 overexpression inhibited tumor cell growth irrespective of p53 status.

Conclusions:

  • NDRG2 is a novel p53-inducible gene.
  • NDRG2 plays a significant role in the p53-mediated apoptotic pathway.
  • NDRG2 functions as a tumor suppressor, impacting cell growth independently of p53.

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