A novel function of Ubc13 in TNFR1 receptor activation

作者：Angermeier Marita; Eckardt Schupp Friederike; Moertl Simone^*

来源：Cellular Signalling, 2010, 22(9): 1388-1396.

DOI：10.1016/j.cellsig.2010.05.009

• TNFR1
• Ubc13
• UV irradiation
• Apoptosis

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.

• 出版日期2010-9