- 作者: Carolyn A. Rankin Claudio A.P. Joazeiro Erik Floor Tony Hunter
- 作者服務機構: The University of Kansas, Higuchi Biosciences Center and Molecular Biosciences Department, lawrence, Kans., Genomics Institute of the Novartlis Research Foundation, San Diego, Calif., The Salk Institute, Molecular Biology and Virology Laboratory, La Jolla, Calif., USA
- 中文摘要: --
- 英文摘要: The parkin gene codes for a 465-amino acid protein which,when mutated, results in autosomal recessive juvenile par-kinsonism (AR-JP). Symptoms of AR-JP are similar tothose of idiopathic Parkinson's disease, with the notableexception being the early onset of AR-JP. We have clonedand expressed human Parkin in Escherichia coli and haveexamined Parkin-mediated ubiquitination in an in vitroubiquitination assay using purified recombinant proteins.We found that Parkin has E3 ubiquitin ligase activity in thissystem, demonstrating for the first time that the E3 activityis an intrinsic function of the Parkin protein and does notrequire posttranslational modification or association withcellular proteins other than an E2 (human Ubc4 E2 was uti-lized in this ubiquitination assay). Mutagenesis of individu-al elements of the conserved RING TRIAD domain indi-cated that at leasttwo elementswere required for ubiquitinligase activity and suggested a functional cooperation be-tween the RING finger elements. Since the activity assayswere conducted with recombinant proteins purified fromE. coli, this is the first time TRIAD element interaction hasbeen demonstrated as an intrinsic feature of Parkin E3activity.
- 中文關鍵字: --
- 英文關鍵字: Parkin. Parkinson's disease. Proteasome. RING finger. TRIAD/RIR domain