A novel function of Ubc13 in TNFR1 receptor activation.
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.
Angermeier
Marita
M
Institute of Radiation Biology, Helmholtz Centre Munich, German Research Centre for Environmental Health, Ingolstaedter Landstrasse 1, Neuherberg, Germany.
Eckardt-Schupp
Friederike
F
Moertl
Simone
S
D017209:Apoptosis; D053181:Caspase 8 / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D034622:RNA Interference; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D014466:Ultraviolet Rays
D016328:NF-kappa B; D047888:Receptors, Tumor Necrosis Factor, Type I; C471607:UBE2N protein, human; D044763:Ubiquitin-Conjugating Enzymes; D053181:Caspase 8