cIAP1,2:TRAF2:TRAF3:NIK complex binds TNFR2 trimer

Stable Identifier
R-HSA-5668417
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Reaction
Species
Homo sapiens
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Tumor necrosis factor receptor 2 (TNFR2) signalling starts with recruitment of the adaptor protein TNF receptor-associated factor 2 (TRAF2) to the intracellular TRAF-binding motif and consequently to indirect recruitment of the TRAF2 associated proteins cellular inhibitors of apoptosis 1 and 2 (cIAP1 and cIAP2), along with a complex of TRAF3 and NF-kB-inducing kinase (NIK) which already interact with TRAF2 in unstimulated cells (Song & Donner. 1994, Rothe et al. 1995, Rothe et al. 1994). In resting cells usually NIK is targeted for ubiquitination and proteasomal degradation however in stimulated cells NIK escapes the ubiquitination by the cIAP1,2:TRAF2::TRAF3 complex due to rapid degradation of TRAF3.

Literature References
PubMed ID Title Journal Year
7639698 Association of a RING finger protein with the cytoplasmic domain of the human type-2 tumour necrosis factor receptor

Song, HY, Donner, DB

Biochem. J. 1995
8702708 Anatomy of TRAF2. Distinct domains for nuclear factor-kappaB activation and association with tumor necrosis factor signaling proteins

Rothe, M, Takeuchi, M, Goeddel, DV

J. Biol. Chem. 1996
19815541 TRAF2 must bind to cellular inhibitors of apoptosis for tumor necrosis factor (tnf) to efficiently activate nf-{kappa}b and to prevent tnf-induced apoptosis

Vaux, DL, Wong, WW, Day, CL, Davidson, AJ, Feltham, R, Pantaki, D, Silke, J, Walczak, H, Lee, EF, Vince, JE, Callus, BA, Carter, H, Gentle, IE, Schmukle, AC, Cordier, SM, Mace, PD

J. Biol. Chem. 2009
25152365 TRAF-mediated modulation of NF-kB AND JNK activation by TNFR2

Ugarte, L, Cabal-Hierro, L, Artime, N, Lazo, PS, Rodríguez, M, Prado, MA, Iglesias, J

Cell. Signal. 2014
7544915 TRAF2-mediated activation of NF-kappa B by TNF receptor 2 and CD40

Sarma, V, Rothe, M, Dixit, VM, Goeddel, DV

Science 1995
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