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A novel function of Ubc13 in TNFR1 receptor activation.
Cell. Signal. 22, 1388-1396 (2010)
The tumour necrosis factor receptor 1 (TNFR1) activates prosurvival pathways by induction of the NFkappaB pathway and induces cell death via apoptosis. The ubiquitin-conjugating enzyme, Ubc13, mediates the ubiquitylation-dependent formation of protein complexes crucial for the activation and regulation of both pathways. We describe a new role for Ubc13 in the regulation of TNFR1 activity after UV stimulation. Depletion of Ubc13 by RNAi produced a decreased NFkappaB activity and increased apoptosis after stimulation by TNFalpha and UV-C light. These results are consistent with the function of Ubc13 in the ubiquitylation of RIP1, which controls the proapoptotic or prosurvival response after TNFR1 activation. Moreover, we demonstrated that UV-C light induces a close interaction between the Ubc13 protein and the TNFR1 receptor. In the absence of Ubc13 TNFR1 clustering was increased. We conclude that Ubc13 has a regulatory role for the activation of TNFR1 and hence, apoptotic cell death. Thus, our results elucidated a new role for Ubc13 in the regulation of prosurvival or proapoptotic processes, which is upstream of so far investigated functions.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
TNFR1; Ubc13; UV irradiation; Apoptosis
Language
english
Publication Year
2010
HGF-reported in Year
2010
ISSN (print) / ISBN
0898-6568
e-ISSN
0898-6568
Journal
Cellular Signalling
Quellenangaben
Volume: 22,
Issue: 9,
Pages: 1388-1396
Publisher
Elsevier
Reviewing status
Peer reviewed
Institute(s)
Institute of Radiation Biology (ISB)
POF-Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
PSP Element(s)
G-500200-002
PubMed ID
20472056
Scopus ID
77953688431
Erfassungsdatum
2010-12-10