Nuclear pore component Nup98 is a potential tumor suppressor and regulates posttranscriptional expression of select p53 target genes.
Mol Cell
; 48(5): 799-810, 2012 Dec 14.
Article
in En
| MEDLINE
| ID: mdl-23102701
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.
Full text:
1
Database:
MEDLINE
Main subject:
RNA, Messenger
/
RNA Processing, Post-Transcriptional
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Tumor Suppressor Protein p53
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Carcinoma, Hepatocellular
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Nuclear Pore Complex Proteins
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Liver Neoplasms
Language:
En
Year:
2012
Type:
Article