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The short splice form of Casper/c‐FLIP is a major cellular inhibitor of TRAIL‐induced apoptosis
Author(s) -
Bin Lianghua,
Li Xiaoyan,
Xu Liang-Guo,
Shu Hong-Bing
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)03222-7
Subject(s) - apoptosis , flip , tumor necrosis factor alpha , inhibitor of apoptosis domain , cancer cell , biology , inhibitor of apoptosis , microbiology and biotechnology , cancer research , cancer , programmed cell death , chemistry , genetics , caspase , immunology
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.