Ludwig-Maximilians-Universität, Chair of Metabolic Biochemistry

Breadcrumb Navigation


Parkin mediates neuroprotection through activation of IkappaB kinase/nuclear factor-kappaB signaling

J Neurosci 27(8): 1868-78

Authors/Editors: Henn IH
Bouman L
Schlehe JS
Schramm JE
Wegener E
Nakaso K
Culmsee C
Berninger B
Krappmann D
Winklhofer KF
Publication Date: 2007
Type of Publication: Journal Article
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 IkappaB kinase (IKK)/nuclear factor kappaB (NF-kappaB) pathway. Our analysis revealed that activation of this signaling cascade is causally linked to the neuroprotective potential of parkin. Inhibition of NF-kappaB activation by an IkappaB super-repressor or a kinase-inactive IKKbeta interferes with the neuroprotective activity of parkin. Furthermore, pathogenic parkin mutants with an impaired neuroprotective capacity show a reduced ability to stimulate NF-kappaB-dependent transcription. Finally, we present evidence that parkin interacts with and promotes degradation-independent ubiquitylation of IKKgamma/NEMO (NF-kappaB essential modifier) and TRAF2 [TNF (tumor necrosis factor) receptor-associated factor 2], two critical components of the NF-kappaB pathway. Thus, our results support a direct link between the neuroprotective activity of parkin and ubiquitin signaling in the IKK/NF-kappaB pathway.

Related Links