Caspase-3-mediated cleavage of the NF-κB subunit p65 at the NH2 terminus potentiates naphthoquinone analog-induced apoptosis
Caspase-3-mediated cleavage of the NF-κB subunit p65 at the NH2 terminus potentiates naphthoquinone analog-induced apoptosis
复制标题
DOI：
10.1074/jbc.m101291200
复制
发表时间：
2001-07-06
影响因子：
4.8
通讯作者：
Choi, KH
中科院分区：
文献类型：
--
作者：
Kang, KH;Lee, KH;Choi, KH
转录因子核因子KB（NF-KB）在免疫和炎症反应中起着至关重要的作用，并保护细胞免于凋亡。在本报告中，我们研究了萘醌类似物2,3-二氯-5,8-二羟基-1,4-萘醌（NA）诱导细胞凋亡过程中NF-KB信号通路是否被阻断，观察到NA触发HeLa细胞中的凋亡细胞死亡，并破坏肿瘤坏死引起的细胞凋亡抵抗力因子-α。 Bata 在这项研究中提出，p65/Re1A（NF-KB 的一个亚基）在细胞凋亡过程中被 caspase-3 在 Asp(97) 处切割，Caspase-3 切割的 p65 失去转录活性并增强 NA 诱导的细胞凋亡，与 p65 的不可切割突变体相反，它可以保护细胞免于细胞凋亡，负责 p65 切割的 Caspase-3 通过在 NA 诱导的细胞凋亡过程中，细胞色素 c/caspase-9 信号通路而不是 Fas/caspase-8 通路，我们的结果表明 NA 通过 caspase-3 介导的 p65 裂解负向调节细胞存活来诱导细胞凋亡。
The transcription factor nuclear factor KB (NF-KB) plays a crucial role in immune and inflammatory response, and protects cells from apoptosis, In this report, we investigate whether the NF-KB signaling pathway is blocked during apoptosis induced by 2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (NA), an analog of naphthoquinone, It is observed that NA triggers apoptotic cell death in HeLa cells and destroys resistance to apoptosis caused by tumor necrosis factor-alpha. Bata presented in this study establish that p65/Re1A, a subunit of NF-KB, is cleaved at Asp(97) by caspase-3 during apoptosis, Caspase-3-cleaved p65 loses transcriptional activity and potentiates NA-induced apoptosis, in contrast to an uncleavable mutant of p65, which protects the cell from apoptosis, Caspase-3, which is responsible for the cleavage of p65, is activated via the cytochrome c/caspase-9 signaling pathway rather than Fas/caspase-8 pathway during NA-induced apoptosis, Our results suggest that NA induces apoptosis by the negative regulation of cell survival through caspase-3-mediated cleavage of p65.