Reciprocal amplification of caspase-3 activity by nuclear export of a putative human RNA-modifying protein, PUS10 during TRAIL-induced apoptosis.
Reciprocal amplification of caspase-3 activity by nuclear export of a putative human RNA-modifying protein, PUS10 during TRAIL-induced apoptosis.
复制标题
DOI：
10.1038/cddis.2017.476
复制
发表时间：
2017-10-05
影响因子：
9
通讯作者：
Gupta R
中科院分区：
文献类型：
--
作者：
Jana S;Hsieh AC;Gupta R
Pus10 是一种假尿苷合酶，存在于古细菌和真核生物中，但不存在于细菌和酵母中。有人提出，TRAIL 诱导的细胞凋亡过程中需要人类 PUS10 (DOBI) 基因。我们通过免疫荧光、免疫印迹和多种细胞凋亡指标分析了 PUS10 在 TRAIL 诱导的细胞凋亡中的作用。我们检查了几种 TRAIL 敏感细胞系，还检查了一些用放线菌酮处理后的耐药细胞系。 PUS10主要存在于细胞核中。在细胞凋亡早期，PUS10 通过 CRM1 介导的输出易位至线粒体，同时释放细胞色素 c 和 SMAC。 Caspase-3 是 PUS10 易位所必需的，PUS10 易位通过内在/线粒体途径相互增强 caspase-3 的活性。这表明除了细胞质因子外，核因子也在主要的凋亡途径中具有直接作用。然而，p53 不参与 TRAIL 诱导的 PUS10 运动。 Caspase-3 介导的 PUS10 运动和增强 caspase-3 活性的线粒体内容物的释放为 caspase-3 作用创建了反馈放大回路。因此，PUS10的运动或相互作用的任何缺陷都会降低肿瘤细胞的TRAIL敏感性。
Pus10 is a pseudouridine synthase present in Archaea and Eukarya, but not in Bacteria and yeast. It has been suggested that the human PUS10 (DOBI) gene is needed during TRAIL-induced apoptosis. We analyzed the role of PUS10 in TRAIL-induced apoptosis by immunofluorescence, immunoblotting and several indicators of apoptosis. We examined several TRAIL-sensitive cell lines and we also examined some resistant cell lines after treatment with cycloheximide. PUS10 is mainly present in the nucleus. Early during apoptosis, PUS10 translocates to mitochondria via CRM1-mediated export with the concurrent release of cytochrome c and SMAC. Caspase-3 is required for PUS10 translocation, which reciprocally amplifies the activity of caspase-3 through the intrinsic/mitochondrial pathway. This suggests that in addition to cytoplasmic factors, nuclear factors also have a direct role in the major apoptosis pathways. However, p53 is not involved in TRAIL-induced PUS10 movement. The caspase-3-mediated movement of PUS10 and the release of mitochondrial contents enhancing caspase-3 activity creates a feedback amplification loop for caspase-3 action. Therefore, any defect in the movement or interactions of PUS10 would reduce the TRAIL sensitivity of tumor cells.
登录
查看更多内容
影响因子：
11.4
作者：
Adrain, C;Creagh, EM;Martin, SJ
通讯作者：
Martin, SJ
影响因子：
8
作者：
Hasenjäger, A;Gillissen, B;Daniel, PT
通讯作者：
Daniel, PT
影响因子：
2
作者：
Flusberg, Deborah A.;Sorger, Peter K.
通讯作者：
Sorger, Peter K.
影响因子：
11.4
作者：
Martin, SJ;AmaranteMendes, GP;Green, DR
通讯作者：
Green, DR
DOI：
10.1073/pnas.96.16.9112
发表时间：
1999-08-03
影响因子：
11.1
作者：
Kudo, N;Matsumori, N;Horinouchi, S
通讯作者：
Horinouchi, S