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Open Access Green as soon as Postprint is submitted to ZB.
Parkin Mediates Neuroprotection through Activation of I{kappa}B Kinase/Nuclear Factor-{kappa}B Signaling.
J. Neurosci. 27, 1868-1878 (2007)
Mutations in the parkin gene are a major cause of autosomal recessive Parkinson's disease. Here we show that the E3 ubiquitin ligase parkin activates signaling through the I{kappa}B kinase (IKK)/nuclear factor {kappa}B (NF-{kappa}B) pathway. Our analysis revealed that activation of this signaling cascade is causally linked to the neuroprotective potential of parkin. Inhibition of NF-{kappa}B activation by an I{kappa}B super-repressor or a kinase-inactive IKKß interferes with the neuroprotective activity of parkin. Furthermore, pathogenic parkin mutants with an impaired neuroprotective capacity show a reduced ability to stimulate NF-{kappa}B-dependent transcription. Finally, we present evidence that parkin interacts with and promotes degradation-independent ubiquitylation of IKK{gamma}/NEMO (NF-{kappa}B essential modifier) and TRAF2 [TNF (tumor necrosis factor) receptor-associated factor 2], two critical components of the NF-{kappa}B pathway. Thus, our results support a direct link between the neuroprotective activity of parkin and ubiquitin signaling in the IKK/NF-{kappa}B pathway
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
IKK; NF-{kappa}B; parkin; Parkinson's disease; TRAF; ubiquitin
ISSN (print) / ISBN
0270-6474
e-ISSN
1529-2401
Journal
Journal of Neuroscience
Quellenangaben
Volume: 27,
Issue: 8,
Pages: 1868-1878
Publisher
Society for Neuroscience
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Research Unit Signaling and Translation (SAT)