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Updated: Apr 9, 2026

In Vitro Analysis of E3 Ubiquitin Ligase Function
Published on: May 14, 2021
Emerging roles of Lys63-linked polyubiquitylation in immune responses
1Laboratory of Signal Transduction and Gene Regulation, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
Abstract:
Among all the E2 ubiquitin-conjugating enzymes, Ubc13, which heterodimerizes with Uev1a, specifically mediates lysine 63 (K63)-linked protein polyubiquitylation, a process that does not lead to proteasomal degradation of its substrates. Instead, it plays a key role in signal transduction. Numerous roles of Lys63-linked polyubiquitylation in immune responses have emerged, indicating the importance of this regulatory strategy. Here, we summarize some of the signaling pathways that depend on Lys63-linked polyubiquitylation during innate and adaptive immune responses, with a focus on the underlying molecular mechanisms. In addition, we describe how Ubc13 itself is regulated and outline its function in transforming growth factor β signaling. We discuss the current progress in pharmacological targeting of Ubc13 in inflammatory and autoimmune diseases as well as cancer therapy.
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