Tumor necrosis factor receptor-associated factor-1 enhances proinflammatory TNF receptor-2 signaling and modifies TNFR1-TNFR2 cooperation.
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.
Wicovsky
A
A
Department of Internal Medicine II, Division of Molecular Internal Medicine, University Hospital Würzburg, Würzburg, Germany.
Henkler
F
F
Salzmann
S
S
Scheurich
P
P
Kneitz
C
C
Wajant
H
H
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
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