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NF-kappaB signal triggering and termination by tumor necrosis factor receptor 2.
J Biol Chem. 2011 Jul 01; 286(26):22814-24.JB

Abstract

Tumor necrosis factor receptor 2 (TNFR2) activates transcription factor κB (NF-κB) and c-Jun N-terminal kinase (JNK). The mechanisms mediating these activations are dependent on the recruitment of TNF receptor-associated factor 2 (TRAF2) to the intracellular region of the receptor. TNFR2 also induces TRAF2 degradation. We show that in addition to the well characterized TRAF2 binding motif 402-SKEE-405, the human receptor contains another sequence located at the C-terminal end (amino acids 425-439), which also recruits TRAF2 and activates NF-κB. In addition to that, human TNFR2 contains a conserved region (amino acids 338-379) which is responsible for TRAF2 degradation and therefore of terminating NF-κB signaling. TRAF2 degradation and the lack of NF-κB activation when both TNFR1 and TNFR2 are co-expressed results in an enhanced ability of TNFR1 to induce cell death, showing that the cross-talk between both receptors is of a great biological relevance. Induction of TRAF2 degradation appears to be independent of TRAF2 binding to the receptor. Amino acids 343-TGSSDSS-349 are essential for inducing TRAF2 degradation because deletion mutants of this region or point mutations at serine residues 345 and 346 or 348 and 349 obliterate the ability of TNFR2 to induce TRAF2 degradation.

Authors+Show Affiliations

Departamento de Bioquímica y Biología Molecular and Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, 33071 Oviedo, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21558270

Citation

Rodríguez, Montserrat, et al. "NF-kappaB Signal Triggering and Termination By Tumor Necrosis Factor Receptor 2." The Journal of Biological Chemistry, vol. 286, no. 26, 2011, pp. 22814-24.
Rodríguez M, Cabal-Hierro L, Carcedo MT, et al. NF-kappaB signal triggering and termination by tumor necrosis factor receptor 2. J Biol Chem. 2011;286(26):22814-24.
Rodríguez, M., Cabal-Hierro, L., Carcedo, M. T., Iglesias, J. M., Artime, N., Darnay, B. G., & Lazo, P. S. (2011). NF-kappaB signal triggering and termination by tumor necrosis factor receptor 2. The Journal of Biological Chemistry, 286(26), 22814-24. https://doi.org/10.1074/jbc.M111.225631
Rodríguez M, et al. NF-kappaB Signal Triggering and Termination By Tumor Necrosis Factor Receptor 2. J Biol Chem. 2011 Jul 1;286(26):22814-24. PubMed PMID: 21558270.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NF-kappaB signal triggering and termination by tumor necrosis factor receptor 2. AU - Rodríguez,Montserrat, AU - Cabal-Hierro,Lucía, AU - Carcedo,María Teresa, AU - Iglesias,Juan Manuel, AU - Artime,Noelia, AU - Darnay,Bryant G, AU - Lazo,Pedro S, Y1 - 2011/05/10/ PY - 2011/5/12/entrez PY - 2011/5/12/pubmed PY - 2011/9/10/medline SP - 22814 EP - 24 JF - The Journal of biological chemistry JO - J Biol Chem VL - 286 IS - 26 N2 - Tumor necrosis factor receptor 2 (TNFR2) activates transcription factor κB (NF-κB) and c-Jun N-terminal kinase (JNK). The mechanisms mediating these activations are dependent on the recruitment of TNF receptor-associated factor 2 (TRAF2) to the intracellular region of the receptor. TNFR2 also induces TRAF2 degradation. We show that in addition to the well characterized TRAF2 binding motif 402-SKEE-405, the human receptor contains another sequence located at the C-terminal end (amino acids 425-439), which also recruits TRAF2 and activates NF-κB. In addition to that, human TNFR2 contains a conserved region (amino acids 338-379) which is responsible for TRAF2 degradation and therefore of terminating NF-κB signaling. TRAF2 degradation and the lack of NF-κB activation when both TNFR1 and TNFR2 are co-expressed results in an enhanced ability of TNFR1 to induce cell death, showing that the cross-talk between both receptors is of a great biological relevance. Induction of TRAF2 degradation appears to be independent of TRAF2 binding to the receptor. Amino acids 343-TGSSDSS-349 are essential for inducing TRAF2 degradation because deletion mutants of this region or point mutations at serine residues 345 and 346 or 348 and 349 obliterate the ability of TNFR2 to induce TRAF2 degradation. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/21558270/NF_kappaB_signal_triggering_and_termination_by_tumor_necrosis_factor_receptor_2_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(19)48819-4 DB - PRIME DP - Unbound Medicine ER -