| 靶标 | Receptor-interacting serine/threonine-protein kinase 1, 2.7.11.1, Cell death protein RIP, Receptor-interacting protein 1, RIP-1, Ripk1, Rinp, Rip |
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| 背景 | Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is a ~74 kDa protein. Serine-threonine kinase which is a key regulator of TNF-mediated apoptosis, necroptosis and inflammatory pathways. Exhibits kinase activity-dependent functions that regulate cell death and kinase-independent scaffold functions regulating inflammatory signaling and cell survival. Has kinase-independent scaffold functions: upon binding of TNF to TNFR1, RIPK1 is recruited to the TNF-R1 signaling complex (TNF-RSC also known as complex I) where it acts as a scaffold protein promoting cell survival, in part, by activating the canonical NF-kappa-B pathway. Kinase activity is essential to regulate necroptosis and apoptosis, two parallel forms of cell death: upon activation of its protein kinase activity, regulates assembly of two death-inducing complexes, namely complex IIa (RIPK1-FADD-CASP8), which drives apoptosis, and the complex IIb (RIPK1-RIPK3-MLKL), which drives necroptosis. RIPK1 is required to limit CASP8-dependent TNFR1-induced apoptosis. 1. Newton, K. et al. (2014) Science (New York, N.Y.) 343, 1357-60. PMID: 245578365. Geng, J. et al. (2017) Nature communications 8, 359. PMID: 288425709. Muendlein, HI. et al. (2021) Nature communications 12, 86. PMID: 33397971 |
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