Parkin protein, encoded by the PRKN gene, is a cytosolic E3 ubiquitin ligase that plays a crucial role in maintaining cellular protein homeostasis and mitochondrial quality control. It is involved in the ubiquitination of target proteins, marking them for degradation by the 26S proteasome, and is essential for the process of mitophagy, which helps eliminate damaged mitochondria. Parkin's dysfunction, often due to mutations in the PRKN gene, is linked to autosomal recessive juvenile parkinsonism and is also implicated in the pathogenesis of sporadic Parkinson's disease (PD). Impairment of Parkin's E3 ligase activity leads to the accumulation of misfolded proteins and damaged mitochondria, contributing to neuronal cell death. Parkin has also been identified as a tumor suppressor, with its reduced expression or mutations associated with various cancers. Understanding the regulation of Parkin's activity is crucial for developing therapeutic strategies to treat PD and other related disorders.
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