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pARylome

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pARylation mediated regulation of cancer pathways

Poly(ADP)ribosylation (pARylation) is an important post-translational modification of proteins that affects diverse biological processes such as DNA damage repair, apoptosis and transcription. The conjugation of Poly(ADP)-ribose (... ver más

08/08/2013

ICR

30K€

Presupuesto del proyecto: 30K€

Líder del proyecto

INSTITUTE OF CANCER RESEARCH THE ROYAL CANCER... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2013-08-08 No tenemos la información de la convocatoria

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Líder del proyecto

INSTITUTE OF CANCER RESEARCH THE ROYAL CANCER... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 30K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Poly(ADP)ribosylation (pARylation) is an important post-translational modification of proteins that affects diverse biological processes such as DNA damage repair, apoptosis and transcription. The conjugation of Poly(ADP)-ribose (pADPr) to target proteins is mediated by members of the Poly(ADP)-ribose polymerase (ARTD/PARP) protein family. ADPr can be attached either as a single moiety or as chains forming poly-ADPr polymers (pADPr). The best-studied member of the ARTD/PARP family is ARTD1/PARP1, a DNA nick sensor enzyme that is activated following DNA damage. ARTD1/PARP1 is able to pARylate itself and a number of other protein targets, such as histones and DNA repair proteins, modulating their activity. Another member of this super-family is the telomeric ARTD/PARP, Tankyrase 1 (ARTD5/TNKS1), which plays an important role in maintaining telomere integrity, by pARylating its telomere partner, TRF1. Since the discovery that defects in homologous recombination sensitise cancer cells to PARP inhibitors there has been a renewed interest in ARTD/PARPs as attractive therapeutic targets. Furthermore, similarly to kinases and phosphorylation it seems likely that ARTD/PARPs and pARylation will have significant roles in the controls of a diverse range of cellular mechanisms. Using a combined approach of RNA interference (RNAi), drug treatment and mass spectrometry-based proteomic analysis, I propose to identify and characterise novel mono- and poly-(ADP)ribosylation targets, specific to particular ARTD/PARPs. This will help to resolve how (ADP)r conjugation regulates biological processes and contributes to the survival and maintenance of cancer cells. Moreover, using pathway specific reporter cell lines I will address the specific contribution of mAR/pARylated proteins for the regulation of several cancer-related signalling pathways. Ultimately, these studies will reveal novel and promising pARylation-based therapeutic targets for cancer treatment.

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