Ubc13: the Lys63 ubiquitin chain building machine

Ubc13 is an ubiquitin E2 conjugating enzyme that participates with many different E3 ligases to form lysine 63-linked (Lys63) ubiquitin chains that are critical to signaling in inflammatory and DNA damage response pathways. Recent studies have suggested Ubc13 as a potential therapeutic target for in...

Full description

Saved in:
Bibliographic Details
Published in:Oncotarget 2016-09, Vol.7 (39), p.64471-64504
Main Authors: Hodge, Curtis D, Spyracopoulos, Leo, Glover, J N Mark
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents - therapeutic use
Antineoplastic Agents - therapeutic use
Antiviral Agents - therapeutic use
DNA Damage
DNA Repair
Drug Design
Enzyme Inhibitors - therapeutic use
Humans
Models, Molecular
Molecular Targeted Therapy
Protein Conformation
Protein Processing, Post-Translational
Review
Structure-Activity Relationship
Ubiquitin-Conjugating Enzymes - antagonists & inhibitors
Ubiquitin-Conjugating Enzymes - chemistry
Ubiquitin-Conjugating Enzymes - genetics
Ubiquitin-Conjugating Enzymes - metabolism
Ubiquitination
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Ubc13 is an ubiquitin E2 conjugating enzyme that participates with many different E3 ligases to form lysine 63-linked (Lys63) ubiquitin chains that are critical to signaling in inflammatory and DNA damage response pathways. Recent studies have suggested Ubc13 as a potential therapeutic target for intervention in various human diseases including several different cancers, alleviation of anti-cancer drug resistance, chronic inflammation, and viral infections. Understanding a potential therapeutic target from different angles is important to assess its usefulness and potential pitfalls. Here we present a global review of Ubc13 from its structure, function, and cellular activities, to its natural and chemical inhibition. The aim of this article is to review the literature that directly implicates Ubc13 in a biological function, and to integrate structural and mechanistic insights into the larger role of this critical E2 enzyme. We discuss observations of multiple Ubc13 structures that suggest a novel mechanism for activation of Ubc13 that involves conformational change of the active site loop.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.10948