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Consequently, accurate regulation of the <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content> signaling pathway is crucial for preventing the potent noxious effects of <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>. These pathological conditions include chronic inflammation, septic shock, cachexia and cancer. The <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content> signaling cascade utilizes a complex network of post\u2010translational modifications to control the cellular response following its activation. Next to phosphorylation, the ubiquitination of signaling complex components is probably the most important modification. This process is mediated by a specialist class of enzymes, the ubiquitin ligases. Equally important is the class of dedicated ubiquitin\u2010specific proteases, the deubiquitinases. Together with ubiquitin binding proteins, this ubiquitination\u2013deubiquitination system enables the dynamics of signaling complexes. In <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content> signaling, these dynamics translate into the precise regulation of the induction of gene activation or cell death. 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