World Library  
Flag as Inappropriate
Email this Article

Tumor necrosis factors

Article Id: WHEBN0009913736
Reproduction Date:

Title: Tumor necrosis factors  
Author: World Heritage Encyclopedia
Language: English
Subject: Fas ligand, Biological response modifiers, List of MeSH codes (D12.644), Index of HIV/AIDS-related articles, Outline of immunology
Collection: Cytokines
Publisher: World Heritage Encyclopedia

Tumor necrosis factors

TNF (Tumor Necrosis Factor) family
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
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]


  • Family members 1
  • Examples 2
  • Notes and references 3
  • External links 4

Family members

Nineteen proteins have been identified as part of the TNF family on the basis of sequence, functional, and structural similarities.[7] They include:[8][9][10]

  • Tumor necrosis factor (TNF) (also known as cachectin [11] or TNF alpha)[12][13] is a cytokine that has a wide variety of functions. It can cause cytolysis of certain tumor cell lines; it is involved in the induction of cachexia; it is a potent pyrogen, causing fever by direct action or by stimulation of interleukin-1 secretion; it can stimulate cell proliferation and induce cell differentiation under certain conditions.
  • Lymphotoxin-alpha (LT-alpha) and lymphotoxin-beta (LT-beta), two related cytokines produced by lymphocytes that are cytotoxic for a wide range of tumor cells in vitro and in vivo.[14]
  • T cell antigen gp39 (CD40L), a cytokine that seems to be important in B-cell development and activation.
  • CD27L, a cytokine that plays a role in T-cell activation. It induces the proliferation of co-stimulated T cells and enhances the generation of cytolytic T cells.
  • CD30L, a cytokine that induces proliferation of T cells.
  • FASL, a cell surface protein involved in cell death.[15]
  • 4-1BBL, an inducible T cell surface molecule that contributes to T-cell stimulation.
  • OX40L, a cell surface protein that co-stimulates T cell proliferation and cytokine production.[16]
  • TNF-related apoptosis inducing ligand (TRAIL), a cytokine that induces apoptosis.[17]
Model of hydrogen bond between Asn34 of subunit A and Arg82 of subunit C, produced by M. musculus, based on PDB structure 2TNF. The residues participating the hydrogen bond are shown in stick. The short bond length, 2.84Å, highly suggests a strong hydrogen bond that supports the tertiary structure. Baeyens, KJ et al. (1999).[1] Generated in Chimera.

All these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-alpha/beta) complexes that are recognized by their specific receptors. Strong hydrogen bonds between the monomers stabilize the tertiary structure. One such example is the Asn34-Arg82 hydrogen bond in the M. musculus TNF alpha.[1] The PROSITE pattern for this family is located in a beta-strand in the central section of the protein that is conserved across all members.

All members of the TNF family, with the exception of the secreted lymphotoxin and a proliferation-inducing ligand (APRIL), are type II transmembrane proteins that protrude from immune cells. Such membrane-bound TNF ligands frequently signal back to the immune cells when they contact and bind their cognate receptors on other cells.[7]


Human proteins containing this domain include:

Notes and references

This article incorporates text from the public domain Pfam and InterPro IPR006052

  1. ^ a b c Baeyens KJ, De Bondt HL, Raeymaekers A, Fiers W, De Ranter CJ (April 1999). "The structure of mouse tumour-necrosis factor at 1.4 Å resolution: towards modulation of its selectivity and trimerization". Acta Crystallogr. D Biol. Crystallogr. 55 (Pt 4): 772–8.  
  2. ^ Fransen L, Müller R, Marmenout A, Tavernier J, Van der Heyden J, Kawashima E, Chollet A, Tizard R, Van Heuverswyn H, Van Vliet A (June 1985). "Molecular cloning of mouse tumour necrosis factor cDNA and its eukaryotic expression". Nucleic Acids Res. 13 (12): 4417–29.  
  3. ^ Kriegler M, Perez C, DeFay K, Albert I, Lu SD (April 1988). "A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: ramifications for the complex physiology of TNF". Cell 53 (1): 45–53.  
  4. ^ Sherry B, Jue DM, Zentella A, Cerami A (December 1990). "Characterization of high molecular weight glycosylated forms of murine tumor necrosis factor". Biochem. Biophys. Res. Commun. 173 (3): 1072–8.  
  5. ^ a b Cseh K, Beutler B (September 1989). "Alternative cleavage of the cachectin/tumor necrosis factor propeptide results in a larger, inactive form of secreted protein". J. Biol. Chem. 264 (27): 16256–60.  
  6. ^ Waltenbaugh C, Doan T, Melvold R, Viselli S (2008). Immunology. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 68.  
  7. ^ a b Sun M, Fink PJ (2007). "A new class of reverse signaling costimulators belongs to the TNF family". J Immunol. 179 (7): 4307–12.  
  8. ^ Peitsch MC, Jongeneel CV (February 1993). "A 3-D model for the CD40 ligand predicts that it is a compact trimer similar to the tumor necrosis factors". Int. Immunol. 5 (2): 233–8.  
  9. ^ Farrah T, Smith CA (July 1992). "Emerging cytokine family". Nature 358 (6381): 26.  
  10. ^ Bazan JF (September 1993). "Emerging families of cytokines and receptors". Curr. Biol. 3 (9): 603–6.  
  11. ^ D. CAPUT, et al., Identification of a common nucleotide sequence in the 3'-untranslated region of mRNA molecules specifying inflammatory mediators, Proc. Natl. Acad. Sci. USA 83:1670-1674 Biochemistry, 1986 and references cited)
  12. ^ Beutler B, Cerami A (October 1988). "The history, properties, and biological effects of cachectin". Biochemistry 27 (20): 7575–82.  
  13. ^ Vilcek J, Lee TH (April 1991). "Tumor necrosis factor. New insights into the molecular mechanisms of its multiple actions". J. Biol. Chem. 266 (12): 7313–6.  
  14. ^ Browning JL, Ngam-ek A, Lawton P, DeMarinis J, Tizard R, Chow EP, Hession C, O'Brine-Greco B, Foley SF, Ware CF (March 1993). "Lymphotoxin beta, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface". Cell 72 (6): 847–56.  
  15. ^ Suda T, Takahashi T, Golstein P, Nagata S (December 1993). "Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family". Cell 75 (6): 1169–78.  
  16. ^ Baum PR, Gayle RB, Ramsdell F, Srinivasan S, Sorensen RA, Watson ML, Seldin MF, Baker E, Sutherland GR, Clifford KN (September 1994). "Molecular characterization of murine and human OX40/OX40 ligand systems: identification of a human OX40 ligand as the HTLV-1-regulated protein gp34". EMBO J. 13 (17): 3992–4001.  
  17. ^ Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, Sutherland GR, Smith TD, Rauch C, Smith CA (December 1995). "Identification and characterization of a new member of the TNF family that induces apoptosis". Immunity 3 (6): 673–82.  

External links

  • Tumor Necrosis Factors at the US National Library of Medicine Medical Subject Headings (MeSH)
  • pex1 tumor necrosis factor gene
This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.

Copyright © World Library Foundation. All rights reserved. eBooks from Project Gutenberg are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.