Direct Interaction Between Two Parkinson-related Protein Parkin and PINK1*

Abstract

Parkinson disease (PD) is the common movement disorder. Along with the development of molecular genetics, genes related to the familial forms of Parkinson's disease such as Parkin (PARK2) and phosphatase and tensin homologue deleted on chromosome ten (PTEN)-induced putative kinase 1——PINK1 (PARK6) have been identified. GST pull-down assays were performed to identify which domain of PINK1 interacted with Parkin, and the result showed that Parkin directly interacted with PINK1, and the PINK1 kinase domain interacted with Parkin. Based on these results, then the co-immunoprecipitation technique was used to investigate the possible interaction between Parkin and PINK1 in 293A cells. The results indicated that Parkin stabilized PINK1 by interfering with its degradation via the ubiquitin-mediated proteasomal pathway, and PINK1 decreased level of Parkin by promoting its degradation via the ubiquitin-mediated proteasomal pathway. The results confirmed that Parkin directly interacted with PINK1, and they regulated each other via the ubiquitin-mediated proteasomal pathway.