Tumor necrosis factor alpha (TNF-alpha ), also known as cachectin and TNFSF2, is the prototypic ligand of the TNF superfamily. It is a pleiotropic molecule that plays a central role in inflammation, immune system development, apoptosis, and lipid metabolism [1, 2]. Mouse TNF-alpha consisits of a 35 amino acid (aa) cytoplasmic domain, a 21 aa transmembrane segment, and a 179 aa extracellular domain (ECD) [3]. Within the ECD, mouse TNF-alpha shares 94% aa sequence identity with rat and 70%-77% with bovine, canine, cotton rat, equine, feline, human, porcine, rat, and rhesus TNF-alpha. TNF -alpha is produced by a wide variety of immune, epithelial, endothelial, and tumor cells [1, 2]. TNF-alpha is assembled intracellularly to form a noncovalently linked homotrimer which is expressed on the cell surface [4]. Cell surface TNF-alpha can induce the lysis of neighboring tumor cells and virus infected cells, and it can generate its own downstream cell signaling following ligation by soluble TNFR I [2, 5]. Shedding of membrane bound TNF-alpha by TACE/ ADAM17 releases the bioactive cytokine, a 55 kDa soluble trimer of the TNF-alpha extracellular domain [6-8]. TNF-alpha binds the ubiquitous 55-60 kDa TNF RI [9, 10] and the hematopoietic cell-restricted 80 kDa TNF RII [11, 12], both of which are also expressed as homotrimers [1, 2, 13].
Reference
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