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  Nucleoporin Nup155 is part of the p53 network in liver cancer

Holzer, K., Ori, A., Cooke, A., Dauch, D., Drucker, E., Riemenschneider, P., et al. (2019). Nucleoporin Nup155 is part of the p53 network in liver cancer. Nature Communications, 10: 2147. doi:10.1038/s41467-019-10133-z.

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 Creators:
Holzer, Kerstin1, 2, Author
Ori, Alessandro3, 4, Author
Cooke, Amy5, Author
Dauch, Daniel6, 7, Author
Drucker, Elisabeth1, Author
Riemenschneider, Philip2, Author
Andres-Pons, Amparo4, 8, Author
DiGuilio, Amanda L.9, 10, Author
Mackmull, Marie-Therese4, Author
Baßler, Jochen11, Author
Roessler, Stephanie1, Author
Breuhahn, Kai1, Author
Zender, Lars6, 7, Author
Glavy, Joseph S.9, 12, Author
Dombrowski, Frank2, Author
Hurt, Ed11, Author
Schirmacher, Peter1, Author
Beck, Martin13, Author              
Singer, Stephan1, 2, 4, Author
Affiliations:
1Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany, ou_persistent22              
2Institute of Pathology, University Medicine Greifswald, Greifswald, Germany, ou_persistent22              
3Leibniz-Institute on Aging, Fritz-Lipmann-Institute (FLI), Jena, Germany, ou_persistent22              
4European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany, ou_persistent22              
5European Molecular Biology Laboratory, Directors′ Research Unit, Heidelberg, Germany, ou_persistent22              
6Department of Internal Medicine VIII, University Hospital Tuebingen, Tübingen, Germany, ou_persistent22              
7Translational Gastrointestinal Oncology Group, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany, ou_persistent22              
8Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland, ou_persistent22              
9Department of Chemistry, Chemical Biology and Biomedical Engineering, Stevens Institute of Technology, Hoboken, USA, ou_persistent22              
10Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, USA, ou_persistent22              
11Heidelberg University Biochemistry Center, Heidelberg, Germany, ou_persistent22              
12Department of Pharmaceutical Sciences, Ben and Maytee Fisch College of Pharmacy, University of Texas at Tyler, Tyler, USA, ou_persistent22              
13Department of Molecular Sociology, Max Planck Institute of Biophysics, Max Planck Society, ou_3040395              

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 Abstract: Cancer-relevant signalling pathways rely on bidirectional nucleocytoplasmic transport events through the nuclear pore complex (NPC). However, mechanisms by which individual NPC components (Nups) participate in the regulation of these pathways remain poorly understood. We discover by integrating large scale proteomics, polysome fractionation and a focused RNAi approach that Nup155 controls mRNA translation of p21 (CDKN1A), a key mediator of the p53 response. The underlying mechanism involves transcriptional regulation of the putative tRNA and rRNA methyltransferase FTSJ1 by Nup155. Furthermore, we observe that Nup155 and FTSJ1 are p53 repression targets and accordingly find a correlation between the p53 status, Nup155 and FTSJ1 expression in murine and human hepatocellular carcinoma. Our data suggest an unanticipated regulatory network linking translational control by and repression of a structural NPC component modulating the p53 pathway through its effectors.

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Language(s): eng - English
 Dates: 2018-01-142019-04-162019-05-14
 Publication Status: Published online
 Pages: 13
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41467-019-10133-z
 Degree: -

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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 10 Sequence Number: 2147 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723