Mutations in the Parkin gene are responsible for the majority of autosomal recessive parkinsonism. Parkin is an E3 ubiquitin ligase with a wide neuroprotective activity. It can maintain mitochondrial integrity and prevent cell death under various stress conditions. Recently, Parkin has been shown to be implicated in the mitochondrial quality control by inducing the removal of damaged mitochondria via mitophagy.
During the last few years, Parkin has also been linked to cancer, as mutations in the Parkin gene were found in several cancer types. The cancer studies suggest a role of Parkin as a tumor suppresssor gene (TSG). In contrast, studies from PD research demonstrate an anti-apoptotic effect of Parkin under stress conditions. These two observed activities of Parkin - TSG activity on the one side and neuroprotective activity on the other side - led us to ask the question, if common or different pathways are involved in these seemingly opposing activities of Parkin. One possibility might be that the two activities are regulated by different types of ubiquitination of target molecules, as Parkin is known to be an E3 ubiquitin ligase.
The expected results of this project may help to understand mechanisms related to two common disease entities of high medical relevance – neurodegeneration and cancer. Moreover, insight into the function of Parkin could be of interest to develop novel therapeutic strategies for Parkinson's disease.