Parkin directly modulates 26S proteasome activity

Ji Won Um, Eunju Im, Hyun Jung Lee, Boram Min, Lang Yoo, Jiho Yoo, Hermann Lübbert, Christine Stichel-Gunkel, Hyun Soo Cho, Jong Bok Yoon, Kwang Chul Chung

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Abstract

Parkinson's disease (PD) is a common neurodegenerative disease that involves the deterioration of dopaminergic neurons in the substantia nigra pars compacta. Although the etiology of PD remains poorly understood, recent genetic, postmortem, and experimental evidence shows that abnormal protein accumulation and subsequent aggregate formation are prominent features of both sporadic and familial PD. While proteasome dysfunction is observed in PD, diverse mutations in the parkin gene are linked to early-onset autosomal-recessive forms of familial PD. We demonstrate that parkin, an E3 ubiquitin ligase, activates the 26S proteasome in an E3 ligase activity-independent manner. Furthermore, an N-terminal ubiquitin-like domain within parkin is critical for the activation of the 26S proteasome through enhancing the interaction between 19S proteasomal subunits, whereas the PD-linked R42P mutant abolishes this action. The current findings point to a novel role for parkin for 26S proteasome assembly and suggest that parkin mutations contribute to the proteasomal dysfunction in PD.

Original languageEnglish
Pages (from-to)11805-11814
Number of pages10
JournalJournal of Neuroscience
Volume30
Issue number35
DOIs
Publication statusPublished - 2010 Sep 1

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All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Um, J. W., Im, E., Lee, H. J., Min, B., Yoo, L., Yoo, J., Lübbert, H., Stichel-Gunkel, C., Cho, H. S., Yoon, J. B., & Chung, K. C. (2010). Parkin directly modulates 26S proteasome activity. Journal of Neuroscience, 30(35), 11805-11814. https://doi.org/10.1523/JNEUROSCI.2862-09.2010