IKK antagonizes CD95 ligation-mediated apoptosis by regulating NF-kappaB activity.
IKK antagonizes CD95 ligation-mediated apoptosis by regulating NF-kappaB activity.
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IKK 通过调节 NF-kappaB 活性来拮抗 CD95 连接介导的细胞凋亡。
DOI：
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发表时间：
2007
期刊：
影响因子：
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通讯作者：
Beifen Shen
中科院分区：
文献类型：
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作者：
Anning Lin;Jing Wang;Yan Li;Yuzuru Minemoto;Jiyan Zhang;Beifen Shen
CD 95（Apo 1/Fas）/CD 95配体系统通过触发细胞凋亡在免疫调节和功能的各个方面发挥关键作用。除了细胞凋亡信号通路，CD 95连接还诱导NF-κ B的活化。以前的研究表明，IkappaB激酶（IKK）可能是通过介导NF-κ B激活的细胞存活的关键球员。然而，IKK在CD 95连接介导的细胞凋亡和NF-κ B活化中的作用仍不清楚。在这份报告中，我们表明，表达半胱天冬酶抗性的不可切割IKK β（UCIKK β）突变体抑制CD 95连接介导的细胞死亡在HeLa细胞。此外，CD 95连接诱导IKK β-/-鼠胚胎成纤维细胞（MEF）中比野生型MEF中更多的细胞死亡，尽管IKK在CD 95连接后仅略微活化。用特异性IKK抑制剂NEMO结合域（NBD）肽预处理HeLa细胞可阻断CD 95连接诱导的NF-κ B转录活性。UCIKK β增强了HeLa细胞的基础NF-κ B活性，从而导致在CD 95连接后更高的NF-κ B活性。因此，IKK通过调节NF-κ B活性拮抗CD 95连接介导的细胞凋亡。
The CD95 (Apo1/Fas)/CD95 ligand system plays pivotal roles in various aspects of immune regulation and function by triggering apoptosis. Besides the apoptosis signaling pathway, CD95 ligation also induces the activation of NF-kappaB. Previous studies suggest that IkappaB kinase (IKK) may be a key player in cell survival by mediating NF-kappaB activation. However, the roles of IKK in CD95 ligation-mediated apoptosis and NF-kappaB activation are still not clear. In this report, we show that expression of the caspase-resistant uncleavable IKKbeta (UCIKKbeta) mutant suppressed CD95 ligation-mediated cell death in HeLa cells. Furthermore, CD95 ligation induced much more cell death in IKKbeta-/- murine embryonic fibroblasts (MEFs) than in wild type MEFs, despite that IKK was only marginally activated upon CD95 ligation. Pretreatment of HeLa cells with a specific IKK inhibitor NEMO-binding domain (NBD) peptide blocked CD95 ligation-induced NF-kappaB transcriptional activity. And UCIKKbeta enhanced the basal NF-kappaB activity, and consequently led to higher NF-kappaB activity upon CD95 ligation in HeLa cells. Therefore, IKK antagonizes CD95 ligation-mediated apoptosis by regulating NF-kappaB activity.