HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Ubiquitinating a Deubiquitinase

Protein ubiquitination is an important regulator of numerous cellular processes, including protein degradation, cell cycle progression, and transcriptional regulation. The process is reversible, and deubiquitination plays an important role in regulating ubiquitin-dependent pathways. Removal of ubiquitin is accomplished by deubiquitinating enzymes, which cleave ubiquitin from proteins, peptides, or small molecules. Ubiquitin C-terminal hydrolase-L1 (UCH-L1) is a highly expressed neuronal deubiquitinating enzyme that may be involved in several neurodegenerative diseases and cancer. However, little is known about its specific functions or modes of regulation.

UCH-L1 (gray) is monoubiquitinated (brown) on lysines near its active site.

In this Paper of the Week, Robin K. Meray and Peter T. Lansbury, Jr. show that UCH-L1 is post-translationally modified by the addition of single ubiquitin molecules to lysine residues near its active site. This modification restricts enzyme activity by preventing it from binding to ubiquitinated targets. The authors also found that permanent monoubiquitination, as mimicked by a ubiquitin-UCH-L1 fusion, inhibits the function of UCH-L1. Interestingly, UCH-L1 catalyzes its own deubiquitination. This is one of the first, if not the first, articles to describe monoubiquitin mediating the regulation of ubiquitin binding by a deubiquitinating enzyme.

FOOTNOTES

See referenced article, J. Biol. Chem. 2007, 282, 10567-10575

[More Papers of the Week]