| Mutations in the Parkin gene cause a juvenile-onset for of Parkinson's disease (PD) that is transmitted in an autosomal recessive way. Studies have shown that mutations in parkin account for almost 50% of all juvenile-onset forms of PD, making parkin one of the most studied genes as a causative factor for PD.;Studies have shown that parkin functions as a RING type Ub ligase, thus targeting potentially toxic proteins for degradation in the UPP. Parkin's E3 ligase activity is linked to its C-terminal RING1-IBR-RING2 domain. However, the function of its N-terminal ubiquitin-like domain (Ubl) remains unclear. Here, we present evidence suggesting that parkin's Ubl domain mediates an interaction between parkin and the proteasome, specifically Rpn13, a novel ubiquitin receptor.;Ubiquitin (Ub), a small 76 amino acid protein, can be covalently attached to other proteins. This post-translational modification is used as a signal for degradation in the ubiquitin-proteasome pathway (UPP). Ubiquitination requires the concerted activity of 3 basic enzymes: Ub-activaying enzyme (E1), Ub-conjugating enzyme (E2) and Ub-ligase (E3). |
