Recent advances in tumor necrosis factor and CD40 signaling

doi:10.1016/S0959-437X(96)90008-8

Current Opinion in Genetics & Development

Volume 6, Issue 1, February 1996, Pages 39-44

https://doi.org/10.1016/S0959-437X(96)90008-8 Get rights and content

Abstract

The past year has witnessed remarkable advances in the understanding of signaling by the two TNF (tumor necrosis factor) receptors, TNFR1 and TNFR2, and the related CD40 receptor. Adaptor molecules (termed TRAFs) have been identified that associate with TNFR2 and CD40 and function to modulate the signaling pathways. Significantly, TRAF2 mediates the activation of NF-κB by both receptors. Furthermore, a molecule called TRADD has been identified that associates with the cytoplasmic segment of TNFR1. TRADD, which contains a novel ‘death domain’ that binds to the corresponding death domain in the cytoplasmic segment of TNFR1, can mediate both activation of NF-κB and induction of apoptosis, the two major responses signaled by TNFR1.

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The lack of bedsore formation even in the terminal stages in patients with ALS is considered characteristic.6 Tumor necrosis factor-α (TNF-α) is a major inflammatory cytokine that elicits a wide range of biological responses, including neuronal apoptosis.7 TNF-α mediates its biological effects through activation of two distinct receptors, TNF-R1 and R2.8
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Tumor necrosis factor (TNF), a protein initially characterized by its ability to cause hemorrhagic necrosis in certain transplanted tumors (Carswell et al., 1975), is now understood to be a multifunctional cytokine (Beutler and Cerami, 1988; Old, 1988). Members of the TNF and TNF receptor (TNFR) superfamilies play crucial roles in both innate and adaptive immunity, regulating cell proliferation, differentiation, survival, and death; cytokine production; lymphocyte costimulation; and isotype switching (Almitage, 1994; Tewari and Dixit, 1996). Members of the TNF and TNFR superfamilies can be distinguished on the basis of their function and expression patterns, despite a partial overlap (Collette et al., 2003).
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Recent advances in tumor necrosis factor and CD40 signaling

Abstract

Immunol Today

Cell

J Biol Chem

Cell

Cell

Cell

Cell

Nature

J Biol Chem

Nature

J Biol Chem

Cell

J Biol Chem

Science

Science

EMBO J

J Immunol

J Exp Med

Science

Immunity

Unraveling function in the TNF ligand and receptor families

Science

The CD40 antigen and its ligand

Annu Rev Immunol

Tumor necrosis factor receptor-mediated signaling pathways

J Cell Biol

Function and activation of NF-kappa B in the immune system

Annu Rev Immunol

Structure, regulation and function of NF-kappa B

Annu Rev Cell Biol

Involvement of the tumor necrosis factor receptor p75 in mediating cytotoxicity and gene regulating activities

Eur J Immunol