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TNF-induced signaling in apoptosis
1School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Abstract:
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 implicated 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.
Insights
Tumor Necrosis Factor (TNF) potently induces apoptosis by activating survival and death pathways. This review focuses on the apoptotic cascade initiated by TNF, primarily through type I receptors.
Area of Science:
- Cellular Biology
- Molecular Biology
- Immunology
Background:
- Tumor Necrosis Factor (TNF) is a key cytokine in the TNF superfamily, known for its potent role in inducing apoptosis.
- TNF simultaneously activates both cell-survival and cell-death signaling pathways within cells.
- NF-kB-dependent genes mediate survival effects, while caspases mediate apoptotic effects of TNF.
Purpose of the Study:
- To review the proteins constituting the primary apoptotic cascade induced by TNF.
- To elucidate the signaling mechanisms underlying TNF-induced apoptosis.
- To focus on the role of type I TNF receptors in initiating apoptosis.
Main Methods:
- Review of existing literature on TNF signaling pathways.
- Analysis of proteins involved in the TNF-induced apoptotic cascade.
- Focus on type I TNF receptor-mediated signaling.
Main Results:
- TNF activates a complex apoptotic cascade primarily through type I receptors.
- The death domain of type I receptors recruits numerous signaling proteins.
- This cascade explains a significant portion of TNF-induced apoptosis but not all implicated factors.
Conclusions:
- The apoptotic cascade is central to TNF-induced cell death, particularly via type I receptors.
- Further research is needed to integrate other factors like reactive oxygen species and ceramide into the apoptosis model.
- Understanding this cascade is crucial for comprehending TNF's role in cellular regulation and disease.