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

被引：61
作者：
Bin, LH
Li, XY
Xu, LG
Shu, HB
机构：
[1] Univ Colorado, Hlth Sci Ctr, Natl Jewish Med & Res Ctr, Dept Immunol, Denver, CO 80206 USA
[2] Univ Colorado, Hlth Sci Ctr, Natl Jewish Med & Res Ctr, CU Canc Ctr, Denver, CO 80206 USA
[3] Peking Univ, Coll Life Sci, Dept Cell Biol & Genet, Beijing 100871, Peoples R China
来源：
FEBS LETTERS | 2002年 / 510卷 / 1-2期
关键词：
TNF-related apoptosis-inducing ligand; Casper-S/c-FLIPs; apoptosis; functional cloning; inhibitor;
D O I：
10.1016/S0014-5793(01)03222-7
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
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页码：37 / 40
页数：4
相关论文
共 22 条
[1]  
Abe K, 2000, ANN NY ACAD SCI, V926, P52
[2]   Safety and antitumor activity of recombinant soluble Apo2 ligand [J].
Ashkenazi, A ;
Pai, RC ;
Fong, S ;
Leung, S ;
Lawrence, DA ;
Masters, SA ;
Blackie, C ;
Chang, L ;
McMurtrey, AE ;
Hebert, A ;
DeForge, L ;
Koumenis, IL ;
Lewis, D ;
Harris, L ;
Bussiere, J ;
Koeppen, H ;
Shahrokh, Z ;
Schwall, RH .
JOURNAL OF CLINICAL INVESTIGATION, 1999, 104 (02) :155-162
[3]   Control of apoptosis by Rel/NF-κB transcription factors [J].
Barkett, M ;
Gilmore, TD .
ONCOGENE, 1999, 18 (49) :6910-6924
[4]   Rel/NF-κB transcription factors protect against tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis by up-regulating the TRAIL decoy receptor DcR1 [J].
Bernard, D ;
Quatannens, B ;
Vandenbunder, B ;
Abbadie, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (29) :27322-27328
[5]  
Griffith TS, 1998, J IMMUNOL, V161, P2833
[6]   TRAIL: a molecule with multiple receptors and control mechanisms [J].
Griffith, TS ;
Lynch, DH .
CURRENT OPINION IN IMMUNOLOGY, 1998, 10 (05) :559-563
[7]   Tumor necrosis factor-related apoptosis-inducing ligand receptors signal NF-κB and JNK activation and apoptosis through distinct pathways [J].
Hu, WH ;
Johnson, H ;
Shu, HB .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (43) :30603-30610
[8]   Inhibition of death receptor signals by cellular FLIP [J].
Irmler, M ;
Thome, M ;
Hahne, M ;
Schneider, P ;
Hofmann, B ;
Steiner, V ;
Bodmer, JL ;
Schroter, M ;
Burns, K ;
Mattmann, C ;
Rimoldi, D ;
French, LE ;
Tschopp, J .
NATURE, 1997, 388 (6638) :190-195
[9]   TCR-mediated up-regulation of c-FLIPshort correlates with resistance toward CD95-mediated apoptosis by blocking death-inducing signaling complex activity [J].
Kirchhoff, S ;
Müller, WW ;
Krueger, A ;
Schmitz, I ;
Krammer, PH .
JOURNAL OF IMMUNOLOGY, 2000, 165 (11) :6293-6300
[10]   Cellular FLICE-inhibitory protein splice variants inhibit different steps of caspase-8 activation at the CD95 death-inducing signaling complex [J].
Krueger, A ;
Schmitz, I ;
Baumann, S ;
Krammer, PH ;
Kirchhoff, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (23) :20633-20640
123