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ENVERESP SIGNED

Crosstalk between nuclear envelope and DNA Damage Response: Role of nucleoporin TPR in the maintenance of genomic integrity

Total Cost €

0

EC-Contrib. €

0

Partnership

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 ENVERESP project word cloud

Explore the words cloud of the ENVERESP project. It provides you a very rough idea of what is the project "ENVERESP" about.

domain    envelope    patients    oncogenesis    genes    oncogenes    ddr    employing    pore    genome    ependymomas9    profiling    deregulated    progression    imaging    solid    dna    found    detect    checkpoint    each    proto    cancer    genesis    receives    development2    vitro    proteomics    posed    therapies    responsive    networks    interestingly    biological    nuclear    mutagenesis    day    signaling    network    types    silac    terminal    genetics    serves    stability    replication    cells    linked    human    damaged    intracranial    protein    maintenance    damage    tumor    proteomic    met    proteins    body    barrier    chromatin    kinase    tumors    liver    mechanism    survival    technologies    phosphorylated    binding    extensive    fused    molecular    cancer8    threats    repair    nucleoporin    translocated    amplification    their    condensation    previously    treatments    critical    atr    thousands    pediatric    lesions    genomics    optimize    electron    signal    tpr    raf    ing    domains    principles    cell    promoter    leads    mechanistic    region    prevents    atm    microscopy    kinases    mutation    expression    counteract    significantly    shorter    breast   

Project "ENVERESP" data sheet

The following table provides information about the project.

Coordinator
IFOM FONDAZIONE ISTITUTO FIRC DI ONCOLOGIA MOLECOLARE 

Organization address
address: VIA ADAMELLO 16
city: MILANO
postcode: 20139
website: www.ifom-firc.it

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 Italy [IT]
 Total cost 168˙277 €
 EC max contribution 168˙277 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2015
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2016
 Duration (year-month-day) from 2016-04-01   to  2018-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    IFOM FONDAZIONE ISTITUTO FIRC DI ONCOLOGIA MOLECOLARE IT (MILANO) coordinator 168˙277.00

Map

 Project objective

Each cell in the human body receives thousands of DNA lesions per day. To counteract threats posed by DNA damage, cells have evolved an integrated signaling network called the DNA-damage response (DDR). This mechanism allows cells to detect DNA lesions, signal their presence and promote their repair. Mutation of DDR genes, which serves as a biological barrier against tumor progression, leads to cancer development2. A large-scale proteomic analysis of proteins phosphorylated in response to DNA damage by checkpoint kinases ATM and ATR identified extensive protein networks responsive to DNA damage. Interestingly, among the proteins identified to be phosphorylated upon DNA damage were several nuclear pore complex factors including nucleoporin Translocated Promoter Region (TPR)5. TPR was previously linked to cancer since its N-terminal domain has been found fused with the protein kinase domains of various proto-oncogenes such as RAF and MET resulting in human solid tumors. TPR expression level was found deregulated in many types of human tumors such as breast and liver cancer8. Amplification of TPR was also significantly associated with a shorter survival of patients with pediatric intracranial ependymomas9. All these findings support a critical role for TPR in the mechanism of oncogenesis. By employing state-of-the-art proteomics (SILAC), genetics (in vitro mutagenesis), genomics (DNA binding profiling) and imaging (electron microscopy) technologies we will investigate how TPR prevents tumor genesis via its role in the DDR network coordinating DNA repair, DNA replication and chromatin condensation with the nuclear envelope upon DNA damage. Providing mechanistic insight into the role of TPR in DDR and the maintenance of genome stability will not only contribute to our understanding of molecular principles of response to damaged DNA, but will allow us to optimize existing cancer treatments and design new molecular targeted therapies in the future.

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The information about "ENVERESP" are provided by the European Opendata Portal: CORDIS opendata.

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