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Description
I. Abstract and Si2nificance OLPrODOSd Prolect
Mutations in the PARK6 (PINK1) gene cause early-onset recessive Parkinson's disease (PD). PINK! is a
mitochondrial serine/threonine kinase, whose deficiency !eads to mitochondria! abnormalities and dopamine
neuron and muscle degeneration in flies. PINK1 is believed to phosphory!ate specific proteins (substrates) that are
necessary to maintain mitochondria! homeostasis and to protect cells against endogenous and exogenous stress. We
hypothesize that abolishing cellular PINK1 kinase activity will result in decreased or absent phosphorylation
of PINK1 substrates. To investigate this, we have generated mouse embryonic stem cells with a conditional
PINK! gene knockout. The aim of the proposed study is to identify novel PINKJ substrates by comparing the
abundance of phosphoproteins in these cells before and after deletion of the PINK1 gene by Cre-mediated
recombination using quantitative mass spectrometry. Uncovering new PINK! substrates will increase our
understanding of the molecular mechanisms underlying dopamine neuron death and may reveal new targets for PD
therapy.
Status | Finished |
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Effective start/end date | 9/1/08 → 8/31/09 |
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