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AUROMYC SIGNED

N-Myc and Aurora A: From Protein Stability to Chromosome TopologyN-Myc and Aurora A: From Protein Stability to Chromosome TopologyMyc and Aurora A: From Protein Stability to Chromosome Topology

Total Cost €

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EC-Contrib. €

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Partnership

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Project "AUROMYC" data sheet

The following table provides information about the project.

Coordinator
JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG 

Organization address
address: SANDERRING 2
city: WUERZBURG
postcode: 97070
website: http://www.uni-wuerzburg.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Project website https://www.biozentrum.uni-wuerzburg.de/molbio/startseite/
 Total cost 2˙455˙180 €
 EC max contribution 2˙455˙180 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-ADG
 Funding Scheme ERC-ADG
 Starting year 2015
 Duration (year-month-day) from 2015-08-01   to  2020-07-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG DE (WUERZBURG) coordinator 1˙891˙017.00
2    UNIVERSITY OF LEEDS UK (LEEDS) participant 564˙162.00
3    UNIVERSITY OF LEICESTER UK (LEICESTER) participant 0.00

Map

 Project objective

There is an intense interest in the function of human Myc proteins that stems from their pervasive role in the genesis of human tumors. A large body of evidence has established that expression levels of one of three closely related Myc proteins are enhanced in the majority of all human tumors and that multiple tumor entities depend on elevated Myc function, arguing that targeting Myc will have significant therapeutic efficacy. This hope awaits clinical confirmation, since the strategies that are currently under investigation to target Myc function or expression have yet to enter the clinic. Myc proteins are global regulators of transcription, but their mechanism of action is poorly understood. Myc proteins are highly unstable in normal cells and rapidly turned over by the ubiquitin/proteasome system. In contrast, they are stabilized in tumor cells. Work by us and by others has shown that stabilization of Myc is required for tumorigenesis and has identified strategies to destabilize Myc for tumor therapy. This work has also led to the surprising observation that the N-Myc protein, which drives neuroendocrine tumorigenesis, is stabilized by association with the Aurora-A kinase and that clinically available Aurora-A inhibitors can dissociate the complex and destabilize N-Myc. Aurora-A has not previously been implicated in transcription, prompting us to use protein crystallography, proteomics and shRNA screening to understand its interaction with N-Myc. We have now identified a novel protein complex of N-Myc and Aurora-A that provides an unexpected and potentially groundbreaking insight into Myc function. We have also solved the crystal structure of the N-Myc/Aurora-A complex. Collectively, both findings open new strategies to target Myc function for tumor therapy.

 Publications

year authors and title journal last update
List of publications.
2020 Apoorva Baluapuri, Elmar Wolf, Martin Eilers
Target gene-independent functions of MYC oncoproteins
published pages: , ISSN: 1471-0072, DOI: 10.1038/s41580-020-0215-2
Nature Reviews Molecular Cell Biology 2020-04-01
2020 Giacomo Cossa, Isabelle Roeschert, Florian Prinz, Apoorva Baluapuri, Raphael Silveira Vidal, Christina Schülein-Völk, Yun-Chien Chang, Carsten Patrick Ade, Guido Mastrobuoni, Cyrille Girard, Lars Wortmann, Susanne Walz, Reinhard Lührmann, Stefan Kempa, Bernhard Kuster, Elmar Wolf, Dominik Mumberg, Martin Eilers
Localized Inhibition of Protein Phosphatase 1 by NUAK1 Promotes Spliceosome Activity and Reveals a MYC-Sensitive Feedback Control of Transcription
published pages: , ISSN: 1097-2765, DOI: 10.1016/j.molcel.2020.01.008
Molecular Cell 2020-03-11
2019 Apoorva Baluapuri, Julia Hofstetter, Nevenka Dudvarski Stankovic, Theresa Endres, Pranjali Bhandare, Seychelle Monique Vos, Bikash Adhikari, Jessica Denise Schwarz, Ashwin Narain, Markus Vogt, Shuang-Yan Wang, Robert Düster, Lisa Anna Jung, Jens Thorsten Vanselow, Armin Wiegering, Matthias Geyer, Hans Michael Maric, Peter Gallant, Susanne Walz, Andreas Schlosser, Patrick Cramer, Martin Eilers, El
MYC Recruits SPT5 to RNA Polymerase II to Promote Processive Transcription Elongation
published pages: 674-687.e11, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2019.02.031
Molecular Cell 74/4 2020-03-11
2019 Steffi Herold, Jacqueline Kalb, Gabriele Büchel, Carsten P. Ade, Apoorva Baluapuri, Jiajia Xu, Jan Koster, Daniel Solvie, Anne Carstensen, Christina Klotz, Sabrina Rodewald, Christina Schülein-Völk, Matthias Dobbelstein, Elmar Wolf, Jan Molenaar, Rogier Versteeg, Susanne Walz, Martin Eilers
Recruitment of BRCA1 limits MYCN-driven accumulation of stalled RNA polymerase
published pages: 545-549, ISSN: 0028-0836, DOI: 10.1038/s41586-019-1030-9
Nature 567/7749 2020-03-11
2019 Stefanie Schmidt, David Gay, Friedrich Wilhelm Uthe, Sarah Denk, Madelon Paauwe, Niels Matthes, Markus Elmar Diefenbacher, Sheila Bryson, Fiona Clare Warrander, Florian Erhard, Carsten Patrick Ade, Apoorva Baluapuri, Susanne Walz, Rene Jackstadt, Catriona Ford, Georgios Vlachogiannis, Nicola Valeri, Christoph Otto, Christina Schülein-Völk, Katja Maurus, Werner Schmitz, John Raymond Philip Knight
A MYC–GCN2–eIF2α negative feedback loop limits protein synthesis to prevent MYC-dependent apoptosis in colorectal cancer
published pages: 1413-1424, ISSN: 1465-7392, DOI: 10.1038/s41556-019-0408-0
Nature Cell Biology 21/11 2020-03-11
2016 Mark W. Richards, Selena G. Burgess, Evon Poon, Anne Carstensen, Martin Eilers, Louis Chesler, Richard Bayliss
Structural basis of N-Myc binding by Aurora-A and its destabilization by kinase inhibitors
published pages: 13726-13731, ISSN: 0027-8424, DOI: 10.1073/pnas.1610626113
Proceedings of the National Academy of Sciences 113/48 2019-07-04

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