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

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

来源：Molecular Cell, 2012, 48(5): 799-810.

DOI：10.1016/j.molcel.2012.09.020

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%26apos;UTR protects p21 mRNA from degradation by the exosome. An in silico approach revealed another p53 target (14-3-3 sigma) 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.

• 出版日期2012-12-14
• 单位河北医科大学