Tumor necrosis factor receptor 2 signaling induces selective c-IAP1-dependent ASK1 ubiquitination and terminates mitogen-activated protein kinase signaling.

TRAF2 and ASK1 play essential roles in tumor necrosis factor alpha (TNF-alpha)-induced mitogen-activated protein kinase signaling. Stimulation through TNF receptor 2 (TNFR2) leads to TRAF2 ubiquitination and subsequent proteasomal degradation. Here we show that TNFR2 signaling also leads to selective ASK1 ubiquitination and degradation in proteasomes. c-IAP1 was identified as ...
the ubiquitin protein ligase for ASK1 ubiquitination, and studies with primary B cells from c-IAP1 knock-out animals revealed that c-IAP1 is required for TNFR2-induced TRAF2 and ASK1 degradation. Moreover, in the absence of c-IAP1 TNFR2-mediated p38 and JNK activation was prolonged. Thus, the ubiquitin protein ligase activity of c-IAP1 is responsible for regulating the duration of TNF signaling in primary cells expressing TNFR2.
Mesh Terms:
Animals, Cell Line, HeLa Cells, Humans, Inhibitor of Apoptosis Proteins, Jurkat Cells, MAP Kinase Kinase Kinase 5, MAP Kinase Signaling System, Mice, Phosphorylation, Proteasome Endopeptidase Complex, Receptors, Tumor Necrosis Factor, Type II, Signal Transduction, Ubiquitin, p38 Mitogen-Activated Protein Kinases
J Biol Chem
Date: Mar. 16, 2007
Download Curated Data For This Publication
251152
Switch View:
  • Interactions 3