title: Tumor necrosis factor receptor 2 signaling induces selective c-IAP1-dependent ASK1 ubiquitination and terminates mitogen-activated protein kinase signaling.
abstract: 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.
authors.affiliation: Laboratory of Immune Cell Biology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Yongge
authors.initials: Y
authors.lastname: Zhao
authors.forename: Dietrich B
authors.initials: DB
authors.lastname: Conze
authors.forename: John A
authors.initials: JA
authors.lastname: Hanover
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Ashwell
mesh_terms: D000818:Animals; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D019169:Jurkat Cells; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000502:physiology*; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D051034:Inhibitor of Apoptosis Proteins; D047889:Receptors, Tumor Necrosis Factor, Type II; D025801:Ubiquitin; D048051:p38 Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5; D046988:Proteasome Endopeptidase Complex