Ubiquitin, proteasome and parkin

The ubiquitin-proteasome system (UPS) is important for intracellular proteolysis. and is responsible for a diverse array of biologically important cellular processes, such as cell-cycle progression, signaling cascades and developmental programs. This system is also involved in the protein quality control, which maintains the health of the cell. Thus, the UPS provides a clue for understanding of the molecular mechanisms underlying various neurodegenerative diseases. In the last decade. we witnessed a tremendous progress in uncovering the mechanisms of Parkinson's disease (PD). Of the several genes that can cause familial PD, park-in. the causative gene of autosomal recessive juvenile parkinsonism (ARJP), is of a special interest because it encodes an ubiquitin-protein ligase. which covalently attaches ubiquitin to target proteins, designating them for destruction by the proteasome. This review summarizes recent studies on the UPS pathway with a special reference to parkin, focusing on how parkin is linked to the pathogenesis of ARJP. (C) 2004 Elsevier B.V. All rights reserved.