Dominant-negative Fas mutation is reversed by down-expression of c-FLIP

被引:16
作者
Beneteau, Marie [1 ]
Daburon, Sophie [1 ]
Moreau, Jean-Francois [1 ]
Taupin, Jean-Luc [1 ]
Legembre, Patrick [1 ]
机构
[1] Univ Bordeaux 2, CNRS, UMR 5164, Lab Composantes Innees Reponse Immunitaire & Diff, F-33076 Bordeaux, France
关键词
D O I
10.1158/0008-5472.CAN-06-1415
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Fas triggering by agonistic antibodies or by its cognate ligand, FasL, induces apoptotic cell death, whereas mutation in the Fas death domain is associated with lymphoma progression. On prolonged culture in the presence of an agonistic anti-Fas antibody, we raised a Jurkat cell line resistant to agonistic antibodies but still sensitive to soluble FasL, which carried at the heterozygous state, a point mutation into the Fas death domain. Down-modulation of c-FLIP expression reversed the blockade of the Fas pathway. We show that the activation threshold for the Fas receptor is more easily overcome by multimeric Fast than by agonistic antibodies and that the increase of this threshold due to mutation in the Fas death domain can be overcome by acting on a downstream effector of the Fas signal, c-FLIP. These findings put forward a new approach to eradicate Fas-resistant tumor cells.
引用
收藏
页码:108 / 115
页数:8
相关论文
共 38 条
[1]   Molecular ordering of the initial signaling events of CD95 [J].
Algeciras-Schimnich, A ;
Shen, L ;
Barnhart, BC ;
Murmann, AE ;
Burkhardt, JK ;
Peter, ME .
MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (01) :207-220
[2]   Genetic disorders of programmed cell death in the immune system [J].
Bidere, Nicolas ;
Su, Helen C. ;
Lenardo, Michael J. .
ANNUAL REVIEW OF IMMUNOLOGY, 2006, 24 :321-352
[3]   TRAIL receptor-2 signals apoptosis through FADD and caspase-8 [J].
Bodmer, JL ;
Holler, N ;
Reynard, S ;
Vinciguerra, P ;
Schneider, P ;
Juo, P ;
Blenis, J ;
Tschopp, J .
NATURE CELL BIOLOGY, 2000, 2 (04) :241-243
[4]   c-FLIPL is a dual function regulator for caspase-8 activation and CD95-mediated apoptosis [J].
Chang, DW ;
Xing, Z ;
Pan, Y ;
Algeciras-Schimnich, A ;
Barnhart, BC ;
Yaish-Ohad, S ;
Peter, ME ;
Yang, XL .
EMBO JOURNAL, 2002, 21 (14) :3704-3714
[5]   Fas gene mutations in the Canale-Smith syndrome, an inherited lymphoproliferative disorder associated with autoimmunity [J].
Drappa, J ;
Vaishnaw, AK ;
Sullivan, KE ;
Chu, JL ;
Elkon, KB .
NEW ENGLAND JOURNAL OF MEDICINE, 1996, 335 (22) :1643-1649
[6]   DOMINANT INTERFERING FAS GENE-MUTATIONS IMPAIR APOPTOSIS IN A HUMAN AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME [J].
FISHER, GH ;
ROSENBERG, FJ ;
STRAUS, SE ;
DALE, JK ;
MIDDELTON, LA ;
LIN, AY ;
STROBER, W ;
LENARDO, MJ ;
PUCK, JM .
CELL, 1995, 81 (06) :935-946
[7]   Involvement of the CD95 (APO-1/Fas) receptor/ligand system in drug-induced apoptosis in leukemia cells [J].
Friesen, C ;
Herr, I ;
Krammer, PH ;
Debatin, KM .
NATURE MEDICINE, 1996, 2 (05) :574-577
[8]  
Gronbaek K, 1998, BLOOD, V92, P3018
[9]  
Häusler P, 1998, EUR J IMMUNOL, V28, P57, DOI 10.1002/(SICI)1521-4141(199801)28:01<57::AID-IMMU57>3.0.CO
[10]  
2-8