Parkin mediates apparent E2-independent monoubiquitination in vitro and contains an intrinsic activity that catalyzes polyubiquitination.

Abstract

BACKGROUND:

Mutations in the parkin gene, which encodes a ubiquitin ligase (E3), are a major cause of autosomal recessive parkinsonism. Although parkin-mediated ubiquitination was initially linked to protein degradation, accumulating evidence suggests that the enzyme is capable of catalyzing multiple forms of ubiquitin modifications including monoubiquitination, K48- and K63-linked polyubiquitination. In this study, we sought to understand how a single enzyme could exhibit such multifunctional catalytic properties.

METHODS AND FINDINGS:

By means of in vitro ubiquitination assays coupled with mass spectrometry analysis, we were surprised to find that parkin is apparently capable of mediating E2-independent protein ubiquitination in vitro, an unprecedented activity exhibited by an E3 member. Interestingly, whereas full length parkin catalyzes solely monoubiquitination regardless of the presence or absence of E2, a truncated parkin mutant containing only the catalytic moiety supports both E2-independent and E2-dependent assembly of ubiquitin chains.

CONCLUSIONS:

Our results here suggest a complex regulation of parkin's activity and may help to explain how a single enzyme like parkin could mediate diverse forms of ubiquitination.

• Authors: Katherine C M Chew, Noriyuki Matsuda, Keiko Saisho, Grace G Y Lim, Chou Chai, Hui-Mei Tan, Keiji Tanaka, Kah-Leong Lim
• Journal: PloS one (PLoS One) Vol. 6 Issue 5 Pg. e19720 ( 2011) ISSN: 1932-6203 [Electronic] United States
• PMID: 21625422 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ubiquitin
• Ubiquitin-Protein Ligases
• parkin protein

Topics

• Catalysis
• Humans
• Ubiquitin (metabolism)
• Ubiquitin-Protein Ligases (metabolism)
• Ubiquitination