Cloning and characterization of a novel caspase-10 isoform that activates NF-kappa B activity.
Cloning and characterization of a novel caspase-10 isoform that activates NF-kappa B activity.
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DOI：
10.1016/j.bbagen.2007.07.010
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发表时间：
2007-11
期刊：
影响因子：
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通讯作者：
Hui Wang;Pingzhang Wang;Xiao-qiong Sun;Ying Luo;Xin Wang;D. Ma;Jun Wu
中科院分区：
文献类型：
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作者：
Hui Wang;Pingzhang Wang;Xiao-qiong Sun;Ying Luo;Xin Wang;D. Ma;Jun Wu
caspase -10（也称为Mch4和FLICE2）是死亡受体（DR）依赖性凋亡途径中的caspase启动物。到目前为止，已经确定了6个剪接变体（caspase-10a-f）。在这里，我们描述了caspase-10家族的一种新的异构体，称为caspase-10g，它在正常人体组织和各种细胞系中广泛表达。Caspase-10g由247个氨基酸组成，不含大亚基或小亚基。在外显子5和外显子6之间存在一个caspase-10g特异性外显子，这导致蛋白质产物在含有死亡效应域（DED）的原结构域之后不久被截断。我们进一步表明，caspase-10g的过表达以剂量和时间依赖性的方式显著增强NF-κ b活性。此外，与蛋白酶活性caspase-10a不同，caspase-10g在哺乳动物细胞中过表达仅促进轻微的细胞凋亡，对caspase-10a介导的细胞凋亡无影响。综上所述，这些结果表明caspase-10g作为caspase-10的一种新的仅前结构域亚型，可能优先在NF-κB通路中发挥调节作用。
Caspase-10 (also known as Mch4 and FLICE2) is an initiator caspase in the death receptor (DR)-dependent apoptotic pathway. So far six splice variants (caspase-10a–f) have been identified. Here we describe a novel isoform of the caspase-10 family named caspase-10g that is widely expressed in normal human tissues and various cell lines. Caspase-10g consists of 247 amino acids and does not contain the large or small subunit. A caspase-10g-specific exon is present between exon 5 and exon 6, which results in a protein product truncated shortly after the death-effector domain (DED)-containing prodomain. We further show that overexpression of caspase-10g dramatically enhances NF-κB activity in a dose- and time-dependent manner. Moreover, caspase-10g, unlike the protease-active caspase-10a, only promotes slight apoptosis when overexpressed in mammalian cells and it has no effect on caspase-10a-mediated apoptosis. Taken together, these results suggest that caspase-10g, as a novel prodomain-only isoform of caspase-10, may play a regulatory role preferentially in the NF-κB pathways.