Wang S, et al. (2012) a-Synuclein disrupts stress signaling by inhibiting polo-like kinase Cdc5/Plk2. Proc Natl Acad Sci U S A 109(40):16119-24
Abstract: Parkinson disease (PD) results from the slow, progressive loss of dopaminergic neurons in the substantia nigra. Alterations in a-synuclein (aSyn), such as mutations or multiplications of the gene, are thought to trigger this degeneration. Here, we show that aSyn disrupts mitogen-activated protein kinase (MAPK)-controlled stress signaling in yeast and human cells, which results in inefficient cell protective responses and cell death. aSyn is a substrate of the yeast (and human) polo-like kinase Cdc5 (Plk2), and elevated levels of aSyn prevent Cdc5 from maintaining a normal level of GTP-bound Rho1, which is an essential GTPase that regulates stress signaling. The nine N-terminal amino acids of aSyn are essential for the interaction with polo-like kinases. The results support a unique mechanism of PD pathology.
|Status: Published||Type: Journal Article||PubMed ID: 22988096|
Topics addressed in this paper
Number of different genes curated to this paper: 7
- To go to the Locus page for a gene, click on the gene name.