Tumor Necrosis Factor

Title: Tumor Necrosis Factor
Additional Names: TNF
Literature References: Cytokine produced by activated macrophages as part of the cellular immune response. Originally characterized by its selective hemorrhagic necrosis of tumor cells. Identification in the sera of endotoxin treated mice previously sensitized with bacillus Calmette-Guerin (BCG): E. A. Carswell et al., Proc. Natl. Acad. Sci. USA 72, 3666 (1975). Partial purification: S. Green et al., ibid. 73, 381 (1976). Preliminary characterization of murine TNF: T. Haranaka, N. Satomi, Jpn. J. Exp. Med. 51, 191 (1981); F. C. Kull, P. Cuatrecasas, J. Immunol. 126, 1279 (1981); of rabbit TNF: M. R. Ruff, G. E. Gifford, ibid. 125, 1671 (1980); N. Matthews et al., Br. J. Cancer 42, 416 (1980). Identification of macrophages as cellular source of TNF: D. N. Männel et al., Infect. Immun. 30, 523 (1980); N. Santomi et al., Jpn. J. Exp. Med. 51, 317 (1981). Differentiation from interferon: N. Bloksma et al., Cancer Immunol. Immunother. 14, 41 (1982). Cytotoxic effect on the malaria parasite Plasmodium falciparum: C. G. Haidaris et al., Infect. Immun. 42, 385 (1983); A. O. Wozencraft et al., ibid. 43, 664 (1984). Activity against transplanted human and murine tumors in mice: T. Haranaka et al., Int. J. Cancer 34, 263 (1984). Human TNF is a trimer of 3 identical subunits with 157 amino acid residues and mol wt 17,350 Da. Cloning and expression of cDNA for human TNF in E. coli: D. Pennica et al., Nature 312, 724 (1984); T. Shirai et al., ibid. 313, 803 (1985); A. M. Wang et al., Science 228, 149 (1985). Identity with cachectin: B. Buetler, A. Cerami, Nature 320, 584 (1986). Structure: E. Y. Jones et al., ibid. 338, 225 (1989). Preliminary evaluation with interferon-g in metastatic melanoma: S. Retsas et al., Br. Med. J. 298, 1290 (1989). Reviews: M. R. Ruff, G. E. Gifford, Lymphokines 2, 235 (1981); L. J. Old, Sci. Am. 258(5), 59-60, 70-75 (1988).
NOTE: Lymphotoxin, a TNF-like factor produced by lymphocytes has been referred to as TNF-b.
Tung Oil Tungsten Hexafluoride Tungsten Trioxide Tungstic(VI) Acid Tunicamycin

TNF(Tumor Necrosis Factor) family
Mouse Tumor Necrosis Factor Alpha.png
Trimeric structure of TNF alpha, produced by Mus musculus, based on PDB structure 2TNF (1.4 Å Resolution). Different colors represent different monomers. Baeyens, KJ et al. (1999).[1] Figure rendered using FirstGlance Jmol.
Symbol TNF
Pfam PF00229
InterPro IPR006052
SCOP 1tnf
OPM superfamily 357
OPM protein 2hew
PDB 1du3 EBI.jpg
crystal structure of trail-sdr5
Symbol TNF
Pfam PF00229
Pfam clan CL0100
InterPro IPR006052
SCOP 1tnr

Tumor necrosis factors (or the TNF family) refer to a group of cytokines that can cause cell death (apoptosis). The first two members of the family to be identified were:

  • Tumor necrosis factor (TNF), formerly known as TNFα or TNF alpha, is the best-known member of this class. TNF is a monocyte-derived cytotoxin that has been implicated in tumor regression, septic shock, and cachexia.[2][3] The protein is synthesized as a prohormone with an unusually long and atypical signal sequence, which is absent from the mature secreted cytokine.[4] A short hydrophobic stretch of amino acids serves to anchor the prohormone in lipid bilayers.[5] Both the mature protein and a partially processed form of the hormone can be secreted after cleavage of the propeptide.[5]
  • Lymphotoxin-alpha, formerly known as Tumor necrosis factor-beta (TNF-β), is a cytokine that is inhibited by interleukin 10.[6]