title: RIPK1 and RIPK3: critical regulators of inflammation and cell death.
abstract: RIPK1 and RIPK3 (receptor-interacting serine/threonine protein kinases 1/3) interact by virtue of their RIP homotypic interaction motifs to mediate a form of cell death called necroptosis, although mice lacking these kinases have very different phenotypes. RIPK1-deficient mice die soon after birth, whereas RIPK3-deficient mice are healthy. Necroptosis involves cell rupture and is triggered by tumor necrosis factor (TNF), Toll-like receptors (TLRs), or the T cell receptor (TCR) when pro-apoptotic caspase-8 is inhibited. Various mouse models of disease are ameliorated by RIPK3 deficiency, suggesting that necroptosis contributes to pathology. Genetic rescue experiments now reveal why RIPK3-deficient are viable but RIPK1-deficient mice are not. These and other experiments indicate unexpected complexity in the regulation of both apoptosis and necroptosis by RIPK1 and RIPK3.
authors: Physiological Chemistry Department, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: knewton@gene.com.
authors: Kim
authors: K
authors: Newton
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D009336:Necrosis / Q000378:metabolism*; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; C506249:RIPK1 protein, human; C119705:RIPK3 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases
keywords: RIPK1; RIPK3; apoptosis; necroptosis