Chronicles of a death foretold: dual sequential cell death checkpoints in TNF signaling.
The kinase RIP1 wears a coat of many colors during TNF receptor signaling and can regulate both activation of pro-survival NFkB and programmed cell death pathways. In this review, we outline how coating RIP1 with K63-linked ubiquitin chains forms a protective layer that prevents RIP1 from binding apoptotic regulators and serves as an early guard against cell death. Further on, binding of NFkB signaling components to the ubiquitin coat of RIP1 activates long-term pro-survival signaling and forms a more impenetrable suit of armor against cell death. If RIP1 is not decorated with ubiquitin chains it becomes an unstoppable harbinger of bad news: programmed cell death.
Immunology Institute, Mount Sinai School of Medicine, New York, NY, USA. marie.a.odonnell@mssm.edu
Marie Anne
MA
O'Donnell
Adrian T
AT
Ting
D000818:Animals; D016923:Cell Death; D006801:Humans; D008954:Models, Biological; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D054875:Ubiquitination
D014409:Tumor Necrosis Factor-alpha; D053422:Receptor-Interacting Protein Serine-Threonine Kinases