@article{d5a38060fe434635b2733889d3f74e63,
title = "Nuclear Pore Component Nup98 Is a Potential Tumor Suppressor and Regulates Posttranscriptional Expression of Select p53 Target Genes",
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.",
author = "Stephan Singer and Ruiying Zhao and Barsotti, {Anthony M.} and Anette Ouwehand and Mina Fazollahi and Elias Coutavas and Kai Breuhahn and Olaf Neumann and Thomas Longerich and Tobias Pusterla and Powers, {Maureen A.} and Giles, {Keith M.} and Leedman, {Peter J.} and Jochen Hess and David Grunwald and Bussemaker, {Harmen J.} and Singer, {Robert H.} and Peter Schirmacher and Carol Prives",
note = "Funding Information: We thank Ella Freulich, Melissa Lopez-Jones, Juliane Winkler, Helen Mueller, Michaela Bissinger, Andrea Hain, and Eva Eiteneuer for excellent technical assistance; Oleg Laptenko, Will Freed-Pastor, and other members of the Prives Laboratory for helpful suggestions; Gabor Halasz for compiling a nonredundant set of 3′UTR sequences; and Xiang-Jun Lu for implementing and maintaining the REDUCE software suite. S.S. was supported by a fellowship from the German Research Foundation Si-1487/1-1 and SFB/TRR77-C5. J.H. and T.P. were supported by SFB/TRR-A7, K.B. by SFB/TRR-B7, and T.L. and O.N. by SFB/TRR-B5. This research was supported by NIH grant CA77742 to C.P. The imaging services and D.G. were partially supported by NIH GM86217 (to R.H.S.). H.J.B. was supported by NIH grants R01HG003008 and U54CA121852, as well as by a John Simon Guggenheim Foundation Fellowship. M.F. was supported by NIH training grant T32GM082797. ",
year = "2012",
month = dec,
day = "14",
doi = "10.1016/j.molcel.2012.09.020",
language = "English (US)",
volume = "48",
pages = "799--810",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "5",
}