Apoptosis Signaling Via TNFR Death Receptor

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Apoptosis is a cell death mechanism that enables organisms to control cell number in tissues and to eliminate individual cells that threaten the animal's survival. Certain cells have Death Receptors on their surface, which detect the presence of extracellular death signals and then activate cells' apoptotic cascades. Death Receptors belong to the TNF (Tumor Necrosis Factor) gene superfamily and generally can have several functions other than initiating apoptosis.

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Eight members of the Death Receptor family have been characterized to date: TNFR1 (Tumor Necrosis Factor Receptor-1), Fas, DR3 (Death Receptor-3), TRAILR1 (TNF-Related Apoptosis-Inducing Ligand Receptor-1), TRAILR2, DR6, EDAR (Ectodysplasin-A Receptor) and NGFR (Nerve Growth Factor Receptor). These are distinguished by a cytoplasmic component known as the Death Domain. When these receptors are stimulated by corresponding ligands, a number of molecules are recruited to the Death Domain, and subsequently, a signaling cascade is activated.

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Activation of Fas, TRAIL-R1, and TRAIL-R2 is often associated with cell death. However, unless the cell's apoptotic pathway is initiated, TNFR1 stimulation usually promotes cytokine generation, inflammation and cell cycle progression. TNF alpha, a TNFR ligand, is an important cytokine that mediates leukocyte activation.

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Activation of Fas, TRAIL-R1, and TRAIL-R2 is often associated with cell death; however TNFR1 stimulation usually promotes cytokine generation, inflammation, and cell cycle progression, unless the cell's apoptotic pathway is initiated.