TNF receptor family

Yun TJ, Chaudhary PM, Shu GL, Frazer JK, Ewings MK, Schwartz SM, Pascual V, Hood LE, Clark EA (1998) OPG/FDCR-1, a TNF receptor family member, is expressed in lymphoid cells and is up-regulated by ligating CD40. J Immunol 161 6113-6121... 

A link between the pathways controlled by the TNF-receptor family members and the mitochondrial pathway has been identified. It has been shown that caspase-8 can cleave Bid, resulting in the formation of truncated Bid (tBid), a death-inducing member of the Bcl-2 family (Gross et al, 1999 Li et al, 1998 Luo et al., 1998). Bid activation appears not to be essential in cells with high amoimts of caspase-8 in the death receptor complex but may be required to amplify the cascade in cells with low amounts of caspase-8 in the death receptor complex. 

The X-ray crystal structure of the complex of the extracellular domain of the human 55 kDa tumour necrosis factor (TNF) receptor with human TNF-P has been determined at 2.85 A resolution. It provides a model for TNF receptor activation. The complex contains three receptor molecules bound symmetrically to one TNF-P trimer. The TNF-P subunits form a groove into which the receptor is inserted. The structure of the receptor-ligand complex also determines its orientation with respect to the cell membrane. The TNF-receptor structure is likely to be representative of the TNF-receptor family as a whole, including the NGF receptor (see Chapter 1). 

Shao Z, Browning JL, Lee X, Scott ML, Shulga-Morskaya S, Allaire N, Thill G, Levesque M, Sah D, McCoy JM, Murray B, Jung V, Pepinsky RB, Mi S (2005) TAJ/TROY, an orphan TNF receptor family member, binds Nogo-66 receptor 1 and regulates axonal regeneration. Neuron 45 353-359. 

Tumour necrosis factor (TNF) receptor family. The mediators themselves include TNF (a P) and lymphotoxin a, and there are at least four receptor subtypes. 

HSV-1 vims entry is mediated by multiple glycoproteins present in the envelope and is a rather complex process. Initial adhesion to the cellular membrane is mediated by the interaction of gC and gB with glycosaminoglycan heparan sulfate. Subsequently, gD binds to a specific cellular receptor, either a member of the TNF receptor family [herpes vims entry mediator A (HveA)], immunoglobulin superfamily (HveB, HveC), or 3-O-sulfated heparan sulfate. Then, the vims enters the cell through membrane fusion promoted by the gH/gL complex and gB (117). 

Roos A, Claessen N, Weening JJ, Aten J. Enhanced T lymphocyte expression of LFA-1, ICAM-1, and the TNF receptor family member 0X40 in ElgCl2-induced systemic autoimmunity. Scand J Immunol 1996 43 507-518. 

Death receptors Proteins belonging to TNF receptor family that occur on cell surface, and mediate killing by effector cells expressing their cognate ligands. 

Apoptosis can be induced by two pathways the extrinsic pathway starts with an activation of death receptors on the cell surface, which leads to the activation of caspases (Figure 5). Death receptors are a subgroup of the tumor necrosis factor (TNF) receptor family that have an intracellular death domain. Death receptors include CD95, TRAIL-Rl, and TRAIL-R2 (TNF-related apoptosis inducing ligand). The stimulated death receptors activate an adaptor protein FADD (Fas-associated death domain protein), which, in turn, activates the inactive form of caspase-8 (cysteine-aspartyl-specific proteases). Caspase-8 activates pro-caspase-3 and also the protein Bid (a member of the Bcl-2 family) that can stimulate and amplify the intrinsic pathway. 

NO can also act in the modulation of the immune system on the enhancement of tumor-specific immune responses and also in the sensitization of resistant tumor cells to immune-related effector mechanisms by regulating the expression of apoptosis-related genes including those bellowing to the TNF receptor family. 

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