vCLAP, a caspase-recruitment domain-containing protein of equine Herpesvirus-2, persistently activates the Ikappa B kinases through oligomerization of IKKgamma.
vCLAP, a caspase-recruitment domain-containing protein of equine Herpesvirus-2, persistently activates the Ikappa B kinases through oligomerization of IKKgamma.
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vCLAP 是马疱疹病毒 2 的一种含有 caspase 募集结构域的蛋白，通过 IKKgamma 的寡聚化持续激活 Ikappa B 激酶。
DOI：
10.1074/jbc.c000792200
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Alnemri,ES
中科院分区：
文献类型：
--
作者：
Poyet,JL;Srinivasula,SM;Alnemri,ES
vCLAP, the E10 gene product of equine herpesvirus-2, is a caspase-recruitment domain (CARD)-containing protein that has been shown to induce both apoptosis and NF-κB activation in mammalian cells. vCLAP has a cellular counterpart, Bcl10/cCLAP, which is also an activator of apoptosis and NF-κB. Recent studies demonstrated that vCLAP activates NF-κB through an IκB kinase (IKK)-dependent pathway, but the underlying mechanism remains unknown. In this report, we demonstrate that vCLAP associates stably with the IKK complex through direct binding to the C-terminal region of IKKγ. Consistent with this finding, IKKγ was found to be essential for vCLAP-induced NF-κB activation, and the association between vCLAP and the IKK complex induced persistent activation of the IKKs. Moreover, enforced oligomerization of the isolated C-terminal region of vCLAP, which interacts with IKKγ, can trigger NF-κB activation. Finally, substitution of the C-terminal region of IKKγ, which interacts with vCLAP, with the CARD of vCLAP or Bcl10 produced a molecule that was able to activate NF-κB when ectopically expressed in IKKγ-deficient cells. These data suggest that vCLAP-induced oligomerization of IKKγ, which is mediated by the CARD of vCLAP, could be the mechanism by which vCLAP induces activation of NF-κB.
