Activation of the NF-κB pathway by Caspase 8 and its homologs
Activation of the NF-κB pathway by Caspase 8 and its homologs
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DOI：
10.1038/sj.onc.1203812
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发表时间：
2000-09-14
期刊：
影响因子：
8
通讯作者：
Hood, L
中科院分区：
文献类型：
--
作者：
Chaudhary, PM;Eby, MT;Hood, L
半胱天冬酶8是半胱天冬酶级联反应中最接近起始端的半胱天冬酶，并且因其在由肿瘤坏死因子受体（TNFR）家族的各种死亡受体介导的细胞死亡中的作用而为人所知。我们已经发现半胱天冬酶8能够独立于其作为促凋亡蛋白酶的活性来激活核因子κB（NF - κB）通路。这种特性定位于其N末端前结构域，该结构域包含两个同源的死亡效应结构域（DED）。半胱天冬酶10和MRIT（半胱天冬酶8的两个含DED的同源物）能够类似地激活NF - κB通路。半胱天冬酶8前结构域的显性负性突变体能够阻断由半胱天冬酶8、FADD以及TNFR家族的几种死亡受体诱导的NF - κB。半胱天冬酶8能够与已知参与NF - κB通路激活的多种蛋白质相互作用，包括丝氨酸 - 苏氨酸激酶RIP、NIK、IKK1和IKK2。因此，含DED的半胱天冬酶以及半胱天冬酶同源物可能具有超出其在介导细胞死亡中已知作用的功能。
Caspase 8 is the most proximal caspase in the caspase cascade and has been known for its role in the mediation of cell death by various death receptors belonging to the TNFR family. We have discovered that Caspase 8 can activate the NF-kappa B pathway independent of its activity as a pro-apoptotic protease, This property is localized to its N-terminal prodomain, which contains two homologous death effector domains (DEDs). Caspase 10 and MRIT, two DEDs-containing homologs of Caspase 8, can similarly activate the NF-kappa B pathway. Dominantnegative mutants of the Caspase 8 prodomain can block NF-kappa B induced by Caspase 8, FADD and several death receptors belonging to the TNFR family. Caspase 8 can interact with multiple proteins known to be involved in the activation of the NF-kappa B pathway, including the serine-threonine kinases RIP, NIK, IKK1 and IKK2, Thus, DEDs-containing caspases and caspase homolog(s) may have functions beyond their known role in the mediation of cell death.