18
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Reversible monoubiquitination regulates the Parkinson disease-associated ubiquitin hydrolase UCH-L1.

      The Journal of Biological Chemistry
      Animals, COS Cells, Cercopithecus aethiops, Cysteine Endopeptidases, metabolism, Half-Life, Humans, Parkinson Disease, enzymology, Protein Processing, Post-Translational, physiology, Ubiquitin, Ubiquitin Thiolesterase

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Deubiquitinating enzymes (DUBs) are negative regulators of protein ubiquitination and play an important role in ubiquitin-dependent processes. Recent studies have found that diverse cellular mechanisms are employed to control the activity of DUBs. Ubiquitin C-terminal hydrolase-L1 (UCH-L1) is a highly expressed neuronal DUB linked to Parkinson disease; however, little is known about its specific functions or modes of regulation. Here, we demonstrate that UCH-L1 is post-translationally modified by monoubiquitin in cells, at lysine residues near the active site. This modification restricts enzyme activity by preventing binding to ubiquitinated targets, and permanent monoubiquitination, as mimicked by a ubiquitin-UCH-L1 fusion, inhibits UCH-L1 in its capacity to increase free ubiquitin levels in cells. Interestingly, UCH-L1 catalyzes its own deubiquitination in an intramolecular manner, thereby regulating the lifetime of this modification. Our results illustrate monoubiquitination as a reversible regulatory mechanism for DUB activity involving auto-deubiquitination.

          Related collections

          Author and article information

          Comments

          Comment on this article