Nuclear pore component Nup98 is a potential tumor suppressor and regulates posttranscriptional expression of select p53 target genesBiochemistry and Molecular Pharmacology Publications and Presentations
UMMS AffiliationDepartment of Biochemistry and Molecular Pharmacology; RNA Therapeutics Institute
Medical Subject Headings14-3-3 Proteins; 3' Untranslated Regions; Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Binding Sites; Camptothecin; Carcinoma, Hepatocellular; Cell Aging; Cyclin-Dependent Kinase Inhibitor p21; Exosomes; Gene Expression Regulation, Neoplastic; Hep G2 Cells; Humans; Liver Neoplasms; Male; Mice; Mice, Knockout; Nuclear Pore Complex Proteins; P-Glycoproteins; RNA Interference; *RNA Processing, Post-Transcriptional; RNA Stability; RNA, Messenger; Time Factors; Transfection; Tumor Suppressor Protein p53
AbstractThe 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 (14-3-3sigma) 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.
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Citation InformationStephan Singer, Ruiying Zhao, Anthony M. Barsotti, Anette Ouwehand, et al.. "Nuclear pore component Nup98 is a potential tumor suppressor and regulates posttranscriptional expression of select p53 target genes" Vol. 48 Iss. 5 (2012) ISSN: 1097-2765 (Linking)
Available at: http://works.bepress.com/david_grunwald/1/