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Fig. 1 | Military Medical Research

Fig. 1

From: Programmed cell death and its role in inflammation

Fig. 1

Model of TNF receptor signaling regulation of cell fate. Upon the binding of TNF to its receptor TNFR1, RIP1 is recruited to TNFR1 and is subsequently ubiquitinated. The polyubiquitinated RIP1, in turn, binds to NEMO, the regulatory subunit of NF-kB, to promote NF-κB activation, which leads to the induction of pro-survival genes to counter the death signals. Cell survival is a result of this pathway. The polyubiquitinated RIP1 can also migrate to the cytoplasm, where RIP1 is de-ubiquitinated by A20, the de-ubiquitylating enzyme. RIP1 and RIP3 can then form a pro-necrotic complex followed by phosphorylation on both kinases and induction of necroptosis. In circumstances in which caspase-8 is activated, RIP1 and RIP3 can be cleaved by caspase-8, and the pro-necrotic complex is blunted, which stimulates the cell to undergo apoptosis

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