Journal of Clinical Immunology

, Volume 19, Issue 6, pp 350–364 | Cite as

TNF-Induced Signaling in Apoptosis

  • Pramod C. Rath
  • Bharat B. AggarwalEmail author


Out of the almost 17 members of the TNF superfamily, TNF is probably the most potent inducer of apoptosis. TNF activates both cell-survival and cell-death mechanisms simultaneously. Activation of NF-kB-dependent genes regulates the survival and proliferative effects pf TNF, whereas activation of caspases regulates the apoptotic effects. TNF-induced apoptosis is mediated primarily through the activation of type I receptors, the death domain of which recruits more than a dozen different signaling proteins, which together are considered part of an apoptotic cascade. This cascade does not, however, account for the role of reactive oxygen intermediates, ceramide, phospholipases, and serine proteases which are also inplicated in TNF-induced apoptosis. This cascade also does not explain how type II TNF receptors which lack the death domain, induce apoptosis. Nevertheless, this review of apoptosis signaling will be limited to those proteins that makeup the cascade.

Tumor necrosis factor signaling apoptosis 


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Copyright information

© Plenum Publishing Corporation 1999

Authors and Affiliations

  1. 1.School of Life SciencesJawaharlal Nehru UniversityNew DelhiIndia
  2. 2.Cytokine Research Laboratory, Department of Molecular OncologyThe University of Texas M. D. Anderson Cancer CenterHouston

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