Identification of NEEP21, encoding neuron-enriched endosomal protein of 21 kDa, as a transcriptional target of tumor suppressor p53

Int J Oncol. 2010 Nov;37(5):1133-41. doi: 10.3892/ijo_00000765.

Abstract

NEEP21, also designated D4S234E or NSG1, is an endosomal protein expressed in neuronal cells under normal conditions. Here, we report that NEEP21 is a direct transcriptional target gene of the tumor suppressor p53. NEEP21 expression is inducible in non-neuronal human cancer cell lines by exposure to adriamycin, hydrogen peroxide, UV and γ-ray in a p53-dependent manner. Chromatin immunoprecipitation assay indicated that a potential p53-binding site (p53BS) is located in intron 1 of the NEEP21 gene. A reporter assay confirmed that p53BS has p53-responsive activity. The heterologous luciferase gene containing p53BS is also transactivated by p73-β and p63-γ. The introduction of the NEEP21 gene into various cancer cell lines suppressed cell growth. Infection with an adenovirus vector containing NEEP21 induced apoptotic cell death via caspase-3 activation in many cancer cell lines. The expression of NEEP21 mRNA was remarkably induced by γ-ray irradiation in the spleen of p53+/+ mice but not in that of p53-/- mice. These results suggest that NEEP21 may play a critical role in apoptosis as a mediator of p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics*
  • Cell Line, Tumor
  • Cell Separation
  • Chromatin Immunoprecipitation
  • Flow Cytometry
  • Gene Expression
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics*
  • Oligonucleotide Array Sequence Analysis
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcriptional Activation / genetics*
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • Carrier Proteins
  • NSG1 protein, human
  • Nerve Tissue Proteins
  • Tumor Suppressor Protein p53