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Mathematical Model aided understanding of Signal Transduction Pathways at the example of Tumor Necrosis Factor (TNF) signaling

Overview - Project Background - TNF Background - Student Projects

TNF is a pleiotropic cytokine that can elicit a wide range of cellular responses. It is a major mediator of apoptosis as well as of inflammation and immunity. TNF has been implicated in the pathogenesis of a wide spectrum of human diseases, including sepsis, diabetes, cancer, osteoporosis, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel diseases. The wide range of biological responds derives from the interaction of TNF with its two receptors TNFR1 and TNFR2, that initiate several intracellular signal  transductionpathways. The apoptotic pathway engages so-called caspases and finally leads to programmed cell death, where the single cell is killed (programmed to undergo suicide) for the benefit of the organism. The NF-kB pathway activated by TNF counteracts apoptosis by inducing anti-apoptotic molecules. Although many components of the TNF signaling pathways have been identified,  the complex network of interacting signals leading to the decision between cellular life and death is still poorly understood. NF-kB is also responsible for the inflammation responses, and the role of the JNK pathway remains elusive. A short introduction to TNF is provided by a recent short review (download) and an extended introduction to TNF as well as an introduction to molecular biology is available upon request.

Science's Signal Transduction Knowledge Environment (STKE) is providing a schematic and simplified overview over the TNF signaling pathways. Also of interest is the closely related FAS signaling pathway that engages the same apoptotic machinery as TNF does and is understood in more detail.


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