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.
journal_name
Proc Natl Acad Sci U S Aauthors
Fukushima T,Matsuzawa S,Kress CL,Bruey JM,Krajewska M,Lefebvre S,Zapata JM,Ronai Z,Reed JCdoi
10.1073/pnas.0700548104subject
Has Abstractpub_date
2007-04-10 00:00:00pages
6371-6issue
15eissn
0027-8424issn
1091-6490pii
0700548104journal_volume
104pub_type
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