Casper/c-FLIP的短剪接形式是TRAIL诱导的细胞凋亡的主要细胞内抑制剂。

The short splice form of Casper/c-FLIP is a major cellular inhibitor of TRAIL-induced apoptosis.

作者信息

Bin Lianghua, Li Xiaoyan, Xu Liang-Guo, Shu Hong-Bing

机构信息

Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, 1400 Jackson Street, K516c, Denver, CO 80206 USA.

出版信息

FEBS Lett. 2002 Jan 2;510(1-2):37-40. doi: 10.1016/s0014-5793(01)03222-7.

DOI:10.1016/s0014-5793(01)03222-7

PMID:11755527

Abstract

TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a member of the tumor necrosis factor family that selectively induces apoptosis of cancer cells. However, some cancer cells or subpopulations within cancer cell lines are resistant to TRAIL-induced apoptosis. We developed a retroviral cDNA library-based functional cloning approach to unambiguously identify putative inhibitory genes of TRAIL-induced apoptosis. This effort identified the short splice form of Casper/c-FLIP, Casper-S/c-FLIPs, as a major cellular protein that confers resistance to TRAIL-induced apoptosis. Furthermore, we found that Casper deficient embryonic fibroblasts (EFs) were highly sensitive while their wild-type counterparts were completely resistant to TRAIL-induced apoptosis. Retroviral-mediated transduction of Casper-S/c-FLIPs into Casper(-/-) EFs restored resistance to TRAIL. These data suggest that Casper-S/c-FLIPs is a major cellular inhibitor of TRAIL-induced apoptosis.

摘要

肿瘤坏死因子相关凋亡诱导配体（TRAIL）是肿瘤坏死因子家族的成员，可选择性诱导癌细胞凋亡。然而，某些癌细胞或癌细胞系中的亚群对TRAIL诱导的凋亡具有抗性。我们开发了一种基于逆转录病毒cDNA文库的功能克隆方法，以明确鉴定TRAIL诱导凋亡的假定抑制基因。这项工作确定了Casper/c-FLIP的短剪接形式，即Casper-S/c-FLIPs，是赋予对TRAIL诱导凋亡抗性的主要细胞蛋白。此外，我们发现Casper缺陷型胚胎成纤维细胞（EFs）对TRAIL高度敏感，而其野生型对应物对TRAIL诱导的凋亡完全抗性。将Casper-S/c-FLIPs通过逆转录病毒介导转导到Casper（-/-）EFs中可恢复对TRAIL的抗性。这些数据表明Casper-S/c-FLIPs是TRAIL诱导凋亡的主要细胞抑制剂。