Ubiquitin-conjugating Enzyme Ubc13 is a Critical Component of Tnf Receptor-associated Factor (Traf)-mediated Inflammatory Responses.
From: Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
Proceedings of the National Academy of Sciences of the United States of America
- Publish Date: Apr 2007
- ISSN: 0027-8424
- Volume: 104
- Issue: 15
- Pages: 6371-6
- Medium: Print
- Language: English
- Citation (JAMA): Fukushima Toru, Matsuzawa Shu-ichi, Kress Christina L, et al. Ubiquitin-conjugating Enzyme Ubc13 is a Critical Component of Tnf Receptor-associated Factor (Traf)-mediated Inflammatory Responses.. Proc. Natl. Acad. Sci. U.S.A. Apr 2007;104:6371-6
Abstract
Ubc13 is a ubiquitin-conjugating enzyme responsible for noncanonical ubiquitination of TNF receptor-associated factor (TRAF)-family adapter proteins involved in Toll-like receptor and TNF-family cytokine receptor signaling, which are regulators of innate immunity. Gene ablation was used to study the function of Ubc13 in mice. Whereas homozygous ubc13 gene disruption resulted in embryonic lethality, heterozygous ubc13(+/-) mice appeared normal, without alterations in immune cell populations. Haploinsufficient ubc13(+/-) mice were resistant to lipopolysaccharide-induced lethality, and demonstrated reduced in vivo ubiquitination of TRAF6. Macrophages and splenocytes isolated from ubc13(+/-) mice exhibited reduced lipopolysaccharide-inducible cytokine secretion and impaired activation of TRAF-dependent signal transduction pathways (NF-kappaB, JNK, and p38 MAPK). These findings document a critical role for Ubc13 in inflammatory responses and suggest that agents reducing Ubc13 activity could have therapeutic utility.
Mesh Headings (Keywords): Animals, Cells, Cultured, Flow Cytometry, Heterozygote, Immunoblotting, Inflammation, Mice, Signal Transduction, TNF Receptor-Associated Factor 6, Ubiquitin-Conjugating Enzymes
Check for Full Text / PubMed Unique Identifier (PMID): 17404240
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.