title: Emerging roles of Lys63-linked polyubiquitylation in immune responses.
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.
authors.affiliation: Laboratory of Signal Transduction and Gene Regulation, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wu
authors.affiliation: Laboratory of Signal Transduction and Gene Regulation, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Karin
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D006801:Humans; D007113:Immunity, Innate; D008239:Lysine / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; C471607:UBE2N protein, human; C471624:UBE2V1 protein, human; D044763:Ubiquitin-Conjugating Enzymes; D008239:Lysine
keywords: K63-polyubiquitylation; Ubc13; adaptive immunity; innate immunity