Human Tumour Necrosis Factors: Structure and Receptor Interactions

  1. Gregory Bock Organizer and
  2. Joan Marsh
  1. Bharat B. Aggarwal,
  2. Ramani A. Aiyer,
  3. Diane Pennica,
  4. Patrick W. Gray and
  5. David V. Goeddel

Published Online: 28 SEP 2007

DOI: 10.1002/9780470513521.ch4

Ciba Foundation Symposium 131 - Tumour Necrosis Factor and Related Cytotoxins

Ciba Foundation Symposium 131 - Tumour Necrosis Factor and Related Cytotoxins

How to Cite

Aggarwal, B. B., Aiyer, R. A., Pennica, D., Gray, P. W. and Goeddel, D. V. (2007) Human Tumour Necrosis Factors: Structure and Receptor Interactions, in Ciba Foundation Symposium 131 - Tumour Necrosis Factor and Related Cytotoxins (eds G. Bock and J. Marsh), John Wiley & Sons, Ltd., Chichester, UK. doi: 10.1002/9780470513521.ch4

Author Information

  1. Department of Molecular Immunology and Developmental Biology, Genentech, Inc., 460 Point San Bruno Boulevard, South San Francisco, California 94080, USA

Publication History

  1. Published Online: 28 SEP 2007

ISBN Information

Print ISBN: 9780471910978

Online ISBN: 9780470513521

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Keywords:

  • human tumour necrosis factors;
  • receptor interactions;
  • protein sequence information;
  • interferons;
  • antiproliferative effects

Summary

Activation of lymphoid and myeloid cells causes the production of factors cytotoxic to various tumour cell types in vitro and in vivo. We have investigated the biochemistry, molecular biology and mechanism of action of two such factors. The factor derived from a myeloid cell line was named TNF-α (previously referred to as TNF) and that derived from lymphoid cells named TNF-β (previously called lymphotoxin). Both proteins were purified from the conditioned media of the human cell lines and sequenced. Structural information revealed that TNF-α is 157 amino acid residues long and contains one disulphide bond. TNF-β is a glycoprotein of 171 amino acids that contains no cysteine residues. Protein sequence information was used to isolate and characterize cDNAs for TNF-α and TNF-β by recombinant DNA methods. The expression of the cDNAs in Escherichia coli made available large quantities of these proteins for biological studies. The two proteins are 31% identical and 52% homologous to each other. The genes for both cytokines are approximately three kilobases in size and are closely linked on human chromosome six.

TNF-α and TNF-β both bind to various cell types via a single class of high affinity receptors. On most cells the same receptor is recognized by both cytokines. The receptors for TNF-α can be up-regulated by both interferons and lectins. Up-regulation of receptors by interferons is accompanied by synergistic enhancement of the biological response whereas up-regulation by lectins results in an antagonistic response. Besides antiproliferative effects, both cytokines exhibit direct antiviral effects on infection by both DNA and RNA viruses.