Innovating Works

AUROMYC

Financiado
N Myc and Aurora A From Protein Stability to Chromosome Topology N Myc and Auro...
N Myc and Aurora A From Protein Stability to Chromosome Topology N Myc and Aurora A From Protein Stability to Chromosome Topology Myc and Aurora A From Protein Stability to Chromosome Topology 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 relate... 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. ver más
30/04/2021
UNI WUERZBURG
2M€
Duración del proyecto: 69 meses Fecha Inicio: 2015-07-24
Fecha Fin: 2021-04-30

Línea de financiación: concedida

El organismo H2020 notifico la concesión del proyecto el día 2021-04-30
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-ADG-2014: ERC Advanced Grant
Cerrada hace 10 años
Presupuesto El presupuesto total del proyecto asciende a 2M€
Líder del proyecto
JULIUSMAXIMILIANSUNIVERSITAT WURZBURG No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5