Journal
MOLECULAR CELL
Volume 48, Issue 5, Pages 799-810Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2012.09.020
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Funding
- German Research Foundation [Si-1487/1-1, SFB/TRR77-C5, SFB/TRR-A7, SFB/TRR-B7, SFB/TRR-B5]
- NIH [CA77742, GM86217, R01HG003008, U54CA121852, T32GM082797]
- John Simon Guggenheim Foundation Fellowship
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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 (14-3-3 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.
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