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Nuclear pore component Nup98 is a potential tumor suppressor and regulates posttranscriptional expression of select

Stephan Singer1, Ruiying Zhao, Anthony M Barsotti

  • 1Department of Biological Sciences, Columbia University, New York, NY 10027, USA.

Molecular Cell
|October 30, 2012
PubMed

Insights

The nucleoporin Nup98 protein is essential for the expression of p21, a key p53 target gene, by protecting its mRNA from degradation. Reduced Nup98 levels in liver cancer correlate with p21 expression.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Gene Regulation

Background:

  • The p53 tumor suppressor is a critical regulator of cellular processes, controlling numerous target genes.
  • Understanding the precise mechanisms of p53 target gene regulation is crucial for cancer research.

Purpose of the Study:

  • To investigate the role of nucleoporin Nup98 in the regulation of p53 target genes.
  • To elucidate the mechanism by which Nup98 influences p21 expression.

Main Methods:

  • Conventional and single-molecule mRNA analyses were employed.
  • In silico approaches were used to identify additional Nup98-regulated genes.
  • Expression analysis of Nup98 and p21 in hepatocellular carcinoma (HCC) samples.

Main Results:

  • Nup98 is required for the full expression of p21, a p53 pathway effector, but not other p53 targets.
  • Nup98 post-transcriptionally regulates p21 mRNA stability by protecting it from exosome-mediated degradation via its 3'UTR.
  • The p53 target gene 14-3-3σ is also regulated by Nup98.
  • Nup98 expression is decreased in HCC and correlates with p21 levels in patients.

Conclusions:

  • Wild-type Nup98 has a novel function in regulating specific p53 target genes, distinct from its oncogenic fusion protein roles.
  • Nup98-mediated regulation of p21 mRNA stability represents a new layer of control in the p53 pathway.
  • Nup98 dysregulation in HCC suggests a potential role in liver cancer pathogenesis.

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