Thome M, Gaide O, Micheau O, Martinon F, Bonnet D, Gonzalez M, Tschopp J
Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Center, CH-1066 Epalinges, Switzerland.
J Cell Biol. 2001 Mar 5;152(5):1115-22. doi: 10.1083/jcb.152.5.1115.
v-E10, a caspase recruitment domain (CARD)-containing gene product of equine herpesvirus 2, is the viral homologue of the bcl-10 protein whose gene was found to be translocated in mucosa-associated lymphoid tissue (MALT) lymphomas. v-E10 efficiently activates the c-jun NH(2)-terminal kinase (JNK), p38 stress kinase, and the nuclear factor (NF)-kappaB transcriptional pathway and interacts with its cellular homologue, bcl-10, via a CARD-mediated interaction. Here we demonstrate that v-E10 contains a COOH-terminal geranylgeranylation consensus site which is responsible for its plasma membrane localization. Expression of v-E10 induces hyperphosphorylation and redistribution of bcl-10 from the cytoplasm to the plasma membrane, a process which is dependent on the intactness of the v-E10 CARD motif. Both membrane localization and a functional CARD motif are important for v-E10-mediated NF-kappaB induction, but not for JNK activation, which instead requires a functional v-E10 binding site for tumor necrosis factor receptor-associated factor (TRAF)6. Moreover, v-E10-induced NF-kappaB activation is inhibited by a dominant negative version of the bcl-10 binding protein TRAF1, suggesting that v-E10-induced membrane recruitment of cellular bcl-10 induces constitutive TRAF-mediated NF-kappaB activation.
v-E10是马疱疹病毒2的一种含半胱天冬酶募集结构域（CARD）的基因产物，是bcl-10蛋白的病毒同源物，其基因在黏膜相关淋巴组织（MALT）淋巴瘤中发生易位。v-E10能有效激活c-jun氨基末端激酶（JNK）、p38应激激酶和核因子（NF）-κB转录途径，并通过CARD介导的相互作用与其细胞同源物bcl-10相互作用。在此我们证明v-E10含有一个COOH末端的香叶基香叶基化共有位点，该位点负责其质膜定位。v-E10的表达诱导bcl-10从细胞质到质膜的过度磷酸化和重新分布，这一过程依赖于v-E10 CARD基序的完整性。膜定位和功能性CARD基序对v-E10介导的NF-κB诱导都很重要，但对JNK激活不重要，JNK激活反而需要v-E10与肿瘤坏死因子受体相关因子（TRAF）6的功能性结合位点。此外，v-E10诱导的NF-κB激活被bcl-10结合蛋白TRAF1的显性负性形式抑制，这表明v-E10诱导的细胞bcl-10的膜募集诱导了组成性TRAF介导的NF-κB激活。
