PROTEASOME-ADAPTORS

Adapting proteasomes to Proteotoxicity

Coordinatore	TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY    more  Organization address address: TECHNION CITY - SENATE BUILDING city: HAIFA postcode: 32000 contact info Titolo: Mr. Nome: Mark Cognome: Davison Email: send email Telefono: +972 4 829 4854 Fax: +972 4 823 2958
Nazionalità Coordinatore	Israel [IL]
Totale costo	100˙000 €
EC contributo	100˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2007-4-3-IRG
Funding Scheme	MC-IRG
Anno di inizio	2007
Periodo (anno-mese-giorno)	2007-10-01   -   2011-09-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY  Organization address address: TECHNION CITY - SENATE BUILDING city: HAIFA postcode: 32000 contact info Titolo: Mr. Nome: Mark Cognome: Davison Email: send email Telefono: +972 4 829 4854 Fax: +972 4 823 2958	IL (HAIFA)	coordinator	0.00

Mappa

 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

 Obiettivo del progetto (Objective)

'Protein folding plays an important role in a number of neurodegenerative conditions, such as parkinson's, alzheimer's and motor neuron diseases. Accumulating evidence suggests that environmental agents may contribute to the pathology of these common disorders by perturbing protein folding, either directly or indirectly through their effects on cell metabolism. However, little is known how cells adapt to the threat of environmentally-induced proteotoxicity. This study will exploit arsenic as a model for an environmental toxin that adversely affects protein folding and one with important public health hazard affecting multiple organ systems. We recently identified AIRAP as an adaptor of proteasomes, the cell's major protein degradation apparatus. Cellular conditions that impair proteasomal activity such as exposure to arsenite induce expression of AIRAP. Our genetic and biochemical data indicate a protective role for the AIRAP proteasome complex, under protein misfolding conditions. The initial characterization of a second protein, AIRAPL (Q8WV99; a highly homologous protein to AIRAP), has shown AIRAPL to be an additional proteasome adaptor with distinct cellular functions under basal and protein misfolding conditions. RNAi experiments in C. elegans, revealed a protective role for AIRAPL in ageing, a protein misfolding related process. In an effort to understand the cellular functions of AIRAPL, identification of proteins whose degradation depends on AIRAPL will be identified by a proteomic approaches. The emphasis will be to examine the toxic effect of the identified proteins in the biochemical approach and relate them to the ageing process. The goal of this research program is to reduce the cellular adaptations to protein malfolding induced by environmental toxins, to their molecular constituents. This will lay the groundwork for identifying relevant biomarkers of exposure and for future preventive and therapeutic interventions against protein misfolding diseases.'