[PDF][PDF] The death domain kinase RIP mediates the TNF-induced NF-κB signal

MA Kelliher, S Grimm, Y Ishida, F Kuo, BZ Stanger… - Immunity, 1998 - cell.com
MA Kelliher, S Grimm, Y Ishida, F Kuo, BZ Stanger, P Leder
Immunity, 1998cell.com
The death domain serine/threonine kinase RIP interacts with the death receptors Fas and
tumor necrosis receptor 1 (TNFR1). In vitro, RIP stimulates apoptosis, SAPK/JNK, and NF-κB
activation. To define the physiologic role (s) that RIP plays in regulating apoptosis in vivo, we
introduced a rip null mutation in mice through homologous recombination. RIP-deficient
mice appear normal at birth but fail to thrive, displaying extensive apoptosis in both the
lymphoid and adipose tissue and dying at 1–3 days of age. In contrast to a normal thymic …
Abstract
The death domain serine/threonine kinase RIP interacts with the death receptors Fas and tumor necrosis receptor 1 (TNFR1). In vitro, RIP stimulates apoptosis, SAPK/JNK, and NF-κB activation. To define the physiologic role(s) that RIP plays in regulating apoptosis in vivo, we introduced a rip null mutation in mice through homologous recombination. RIP-deficient mice appear normal at birth but fail to thrive, displaying extensive apoptosis in both the lymphoid and adipose tissue and dying at 1–3 days of age. In contrast to a normal thymic anti-Fas responserip−/− cells are highly sensitive to TNFα-induced cell death. Sensitivity to TNFα-mediated cell death in rip−/− cells is accompanied by a failure to activate the transcription factor NF-κB.
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