title: Tumor necrosis factor receptor-associated factor-1 enhances proinflammatory TNF receptor-2 signaling and modifies TNFR1-TNFR2 cooperation.
abstract: It has been shown that tumor necrosis factor receptor-2 (TNFR2) stimulation leads to degradation of TNF receptor associated factor-2 (TRAF2) and inhibition of TNFR1-induced activation of NFkappaB and JNK. Here, we show that TRAF1 inhibits TNFR2-induced proteasomal degradation of TRAF2 and relieves TNFR1-induced activation of NFkappaB from the inhibitory effect of TNFR2. TRAF1 co-recruited with TRAF2 to both TNF receptors. Despite lacking an amino-terminal RING/zinc-finger domain, TRAF1 did not interfere with TNFR1-induced activation of JNK and NFkappaB. It is noted that physiological expression levels of TRAF1 enhanced NFkappaB activation and interleukin-8 (IL8) production induced by TNFR2. Thus, TRAF1 shifts the quality of integrated TNFR1-TNFR2 signaling from apoptosis induction to proinflammatory NFkappaB signaling.
authors.affiliation: Department of Internal Medicine II, Division of Molecular Internal Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Wicovsky
authors.forename: F
authors.initials: F
authors.lastname: Henkler
authors.forename: S
authors.initials: S
authors.lastname: Salzmann
authors.forename: P
authors.initials: P
authors.lastname: Scheurich
authors.forename: C
authors.initials: C
authors.lastname: Kneitz
authors.forename: H
authors.initials: H
authors.lastname: Wajant
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D016328:NF-kappa B / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000502:physiology*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D047990:TNF Receptor-Associated Factor 1 / Q000502:physiology*; D047992:TNF Receptor-Associated Factor 2 / Q000502:physiology
chemical_list: D016209:Interleukin-8; D016328:NF-kappa B; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2