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TRAF2 multitasking in TNF receptor-induced signaling to NF-κB, MAP kinases and cell death.
Biochem Pharmacol. 2016 09 15; 116:1-10.BP

Abstract

Tumor Necrosis Factor (TNF) is a potent inflammatory cytokine that exerts its functions through the activation of two distinct receptors, TNFR1 and TNFR2. Both receptors can activate canonical NF-κB and JNK MAP kinase signaling, while TNFR2 can also activate non-canonical NF-κB signaling, leading to numerous changes in gene expression that drive inflammation, cell proliferation and cell survival. On the other hand, TNFR1 also activates signaling pathways leading to cell death by either apoptosis or necroptosis, depending on the cellular context. A key player in TNFR1- and TNFR2-induced signaling is the RING finger protein TRAF2, which is recruited to both receptors upon their stimulation. TRAF2 exerts multiple receptor-specific functions but also mediates cross-talk between TNFR1 and TNFR2, dictating the outcome of TNF stimulation. In this review, we provide an overview of the positive and negative regulatory role of TRAF2 in different TNFR1 and TNFR2 signaling pathways. We discuss the underlying molecular mechanism of action, distinguishing between TRAF2 scaffold and E3 ubiquitin ligase functions, and the regulation of TRAF2 by specific post-translational modifications. Finally, we elaborate on some possible strategies to modulate TRAF2 function in the context of therapeutic targeting in autoimmunity and cancer.

Authors+Show Affiliations

Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium. Electronic address: Rudi.Beyaert@irc.vib-UGent.be.

Pub Type(s)

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

Language

eng

PubMed ID

26993379

Citation

Borghi, Alice, et al. "TRAF2 Multitasking in TNF Receptor-induced Signaling to NF-κB, MAP Kinases and Cell Death." Biochemical Pharmacology, vol. 116, 2016, pp. 1-10.
Borghi A, Verstrepen L, Beyaert R. TRAF2 multitasking in TNF receptor-induced signaling to NF-κB, MAP kinases and cell death. Biochem Pharmacol. 2016;116:1-10.
Borghi, A., Verstrepen, L., & Beyaert, R. (2016). TRAF2 multitasking in TNF receptor-induced signaling to NF-κB, MAP kinases and cell death. Biochemical Pharmacology, 116, 1-10. https://doi.org/10.1016/j.bcp.2016.03.009
Borghi A, Verstrepen L, Beyaert R. TRAF2 Multitasking in TNF Receptor-induced Signaling to NF-κB, MAP Kinases and Cell Death. Biochem Pharmacol. 2016 09 15;116:1-10. PubMed PMID: 26993379.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TRAF2 multitasking in TNF receptor-induced signaling to NF-κB, MAP kinases and cell death. AU - Borghi,Alice, AU - Verstrepen,Lynn, AU - Beyaert,Rudi, Y1 - 2016/03/16/ PY - 2016/02/14/received PY - 2016/03/14/accepted PY - 2016/3/20/entrez PY - 2016/3/20/pubmed PY - 2017/5/10/medline KW - Apoptosis KW - NF-κB KW - Necroptosis KW - TNF KW - TRAF2 SP - 1 EP - 10 JF - Biochemical pharmacology JO - Biochem Pharmacol VL - 116 N2 - Tumor Necrosis Factor (TNF) is a potent inflammatory cytokine that exerts its functions through the activation of two distinct receptors, TNFR1 and TNFR2. Both receptors can activate canonical NF-κB and JNK MAP kinase signaling, while TNFR2 can also activate non-canonical NF-κB signaling, leading to numerous changes in gene expression that drive inflammation, cell proliferation and cell survival. On the other hand, TNFR1 also activates signaling pathways leading to cell death by either apoptosis or necroptosis, depending on the cellular context. A key player in TNFR1- and TNFR2-induced signaling is the RING finger protein TRAF2, which is recruited to both receptors upon their stimulation. TRAF2 exerts multiple receptor-specific functions but also mediates cross-talk between TNFR1 and TNFR2, dictating the outcome of TNF stimulation. In this review, we provide an overview of the positive and negative regulatory role of TRAF2 in different TNFR1 and TNFR2 signaling pathways. We discuss the underlying molecular mechanism of action, distinguishing between TRAF2 scaffold and E3 ubiquitin ligase functions, and the regulation of TRAF2 by specific post-translational modifications. Finally, we elaborate on some possible strategies to modulate TRAF2 function in the context of therapeutic targeting in autoimmunity and cancer. SN - 1873-2968 UR - https://www.unboundmedicine.com/medline/citation/26993379/TRAF2_multitasking_in_TNF_receptor_induced_signaling_to_NF_κB_MAP_kinases_and_cell_death_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-2952(16)00162-3 DB - PRIME DP - Unbound Medicine ER -