Publication Date:
2006-11-16
Description:
Ubc13 is an ubiquitin-conjugating enzyme responsible for non-canonical ubiquitination of TRAF-family adapter proteins involved in Toll-like Receptor (TLR) and TNF-family cytokine receptor signaling. Gene ablation was used to study the function of Ubc13 in mice. While 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 (LPS)-induced lethality, and demonstrated reduced in vivo ubiquitination of TRAF6. Macrophages and splenocytes isolated from ubc13+/− mice exhibited reduced LPS-inducible cytokine secretion and impaired activation of TRAF-dependent signal transduction pathways (NF-kB, JNK, p38 MAPK). These findings document a critical role for Ubc13 in inflammatory responses, and suggest that agents reducing Ubc13 activity could have therapeutic utility.
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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