Nuclear Pore Component Nup98 Is a Potential Tumor Suppressor and Regulates Posttranscriptional Expression of Select p53 Target Genes

Stephan Singer, Ruiying Zhao, Anthony M. Barsotti, Anette Ouwehand, Mina Fazollahi, Elias Coutavas, Kai Breuhahn, Olaf Neumann, Thomas Longerich, Tobias Pusterla, Maureen A. Powers, Keith M. Giles, Peter J. Leedman, Jochen Hess, David Grunwald, Harmen J. Bussemaker, Robert H. Singer, Peter Schirmacher, Carol Prives

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

The p53 tumor suppressor utilizes multiple mechanisms to selectively regulate its myriad target genes, which in turn mediate diverse cellular processes. Here, using conventional and single-molecule mRNA analyses, we demonstrate that the nucleoporin Nup98 is required for full expression of p21, a key effector of the p53 pathway, but not several other p53 target genes. Nup98 regulates p21 mRNA levels by a posttranscriptional mechanism in which a complex containing Nup98 and the p21 mRNA 3'UTR protects p21 mRNA from degradation by the exosome. An in silico approach revealed another p53 target (14-3-3σ) to be similarly regulated by Nup98. The expression of Nup98 is reduced in murine and human hepatocellular carcinomas (HCCs) and correlates with p21 expression in HCC patients. Our study elucidates a previously unrecognized function of wild-type Nup98 in regulating select p53 target genes that is distinct from the well-characterized oncogenic properties of Nup98 fusion proteins.

Original languageEnglish (US)
Pages (from-to)799-810
Number of pages12
JournalMolecular Cell
Volume48
Issue number5
DOIs
StatePublished - Dec 14 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Singer, S., Zhao, R., Barsotti, A. M., Ouwehand, A., Fazollahi, M., Coutavas, E., Breuhahn, K., Neumann, O., Longerich, T., Pusterla, T., Powers, M. A., Giles, K. M., Leedman, P. J., Hess, J., Grunwald, D., Bussemaker, H. J., Singer, R. H., Schirmacher, P., & Prives, C. (2012). Nuclear Pore Component Nup98 Is a Potential Tumor Suppressor and Regulates Posttranscriptional Expression of Select p53 Target Genes. Molecular Cell, 48(5), 799-810. https://doi.org/10.1016/j.molcel.2012.09.020