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Defining the pathways and mechanism of misfolded protein triage and quality control in eukaryotic cells

Cel

Proteins need to be correctly folded to carry out their biological function. Failure to fold leads to aberrant protein conformations that have an increased tendency to aggregate and have deleterious effect on cell viability. Eukaryotes have developed a sophisticated protein quality control (QC) system that protects cells from misfolded or incompletely synthesized polypeptides that would otherwise interfere with normal cellular functions or even induce cellular death. The QC system may promote refolding of these non-native proteins by molecular chaperones, enhance their degradation by the ubiquitin-proteasome system or autophagy, or terminally sequester these misfolded proteins in inclusion bodies called IPODs. Impairment of the activity of this QC system, for instance due to ageing or disease, is thought to underlie the growing number of age-related aggregation disorders, such as Parkinson, Alzheimer and Huntington disease, all of which are characterized by accumulation of misfolded aggregated proteins. At present, it remains largely elusive how the quality control machinery recognizes misfolded proteins, and how the triage decision is implemented: i.e. why certain misfolded proteins are refolded whereas others are targeted for degradation or sequestered in cellular inclusions. The goal of this project is therefore to identify the played of the QC machinery and define how the interplay between molecular chaperones and degradation pathways maintain cellar protein homeostasis. The proposed work will build on the large body of work of the host laboratories and will combine systems approaches with cell biology and biochemistry to address these important questions.

Zaproszenie do składania wniosków

FP7-PEOPLE-2011-IOF
Zobacz inne projekty w ramach tego zaproszenia

Koordynator

UNIVERSITEIT UTRECHT
Wkład UE
€ 263 660,70
Adres
HEIDELBERGLAAN 8
3584 CS Utrecht
Niderlandy

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Region
West-Nederland Utrecht Utrecht
Rodzaj działalności
Higher or Secondary Education Establishments
Kontakt administracyjny
Ineke Braakman (Prof.)
Linki
Koszt całkowity
Brak danych