Kelliher M A, Grimm S, Ishida Y, Kuo F, Stanger B Z, Leder P
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Immunity. 1998 Mar;8(3):297-303. doi: 10.1016/s1074-7613(00)80535-x.
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-kappaB 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 response, rip-/- cells are highly sensitive to TNFalpha-induced cell death. Sensitivity to TNFalpha-mediated cell death in rip-/- cells is accompanied by a failure to activate the transcription factor NF-kappaB.
死亡结构域丝氨酸/苏氨酸激酶RIP与死亡受体Fas和肿瘤坏死因子受体1（TNFR1）相互作用。在体外，RIP可刺激细胞凋亡、应激激活蛋白激酶/应激活化蛋白激酶（SAPK/JNK）以及核因子κB（NF-κB）的激活。为了确定RIP在体内调节细胞凋亡中所起的生理作用，我们通过同源重组在小鼠中引入了rip无效突变。RIP缺陷型小鼠出生时看似正常，但生长不良，在淋巴组织和脂肪组织中均表现出广泛的细胞凋亡，并在1至3日龄时死亡。与正常的胸腺抗Fas反应相反，rip-/-细胞对肿瘤坏死因子α（TNFα）诱导的细胞死亡高度敏感。rip-/-细胞对TNFα介导的细胞死亡的敏感性伴随着无法激活转录因子NF-κB。
