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Nucleoporin Nup155 is part of the p53 network in liver cancer

Author

Listed:
  • Kerstin Holzer

    (University Hospital Heidelberg
    University Medicine Greifswald)

  • Alessandro Ori

    (Fritz-Lipmann-Institute (FLI)
    Structural and Computational Biology Unit)

  • Amy Cooke

    (Directors′ Research Unit)

  • Daniel Dauch

    (University Hospital Tuebingen
    German Cancer Research Center (DKFZ))

  • Elisabeth Drucker

    (University Hospital Heidelberg)

  • Philip Riemenschneider

    (University Medicine Greifswald)

  • Amparo Andres-Pons

    (Structural and Computational Biology Unit
    Friedrich Miescher Institute for Biomedical Research)

  • Amanda L. DiGuilio

    (Stevens Institute of Technology
    The University of Chicago)

  • Marie-Therese Mackmull

    (Structural and Computational Biology Unit)

  • Jochen Baßler

    (Heidelberg University Biochemistry Center)

  • Stephanie Roessler

    (University Hospital Heidelberg)

  • Kai Breuhahn

    (University Hospital Heidelberg)

  • Lars Zender

    (University Hospital Tuebingen
    German Cancer Research Center (DKFZ))

  • Joseph S. Glavy

    (Stevens Institute of Technology
    University of Texas at Tyler)

  • Frank Dombrowski

    (University Medicine Greifswald)

  • Ed Hurt

    (Heidelberg University Biochemistry Center)

  • Peter Schirmacher

    (University Hospital Heidelberg)

  • Martin Beck

    (Structural and Computational Biology Unit
    Max Planck Institute of Biophysics)

  • Stephan Singer

    (University Hospital Heidelberg
    University Medicine Greifswald
    Structural and Computational Biology Unit)

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.

Suggested Citation

  • Kerstin Holzer & Alessandro Ori & Amy Cooke & Daniel Dauch & Elisabeth Drucker & Philip Riemenschneider & Amparo Andres-Pons & Amanda L. DiGuilio & Marie-Therese Mackmull & Jochen Baßler & Stephanie R, 2019. "Nucleoporin Nup155 is part of the p53 network in liver cancer," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10133-z
    DOI: 10.1038/s41467-019-10133-z
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