Stress-induced Fas ligand expression in T cells is mediated through a MEK kinase 1-regulated response element in the Fas ligand promoter

被引:173
作者
Faris, M
Latinis, KM
Kempiak, SJ
Koretzky, GA
Nel, A
机构
[1] Univ Calif Los Angeles, Sch Med, Dept Med, Div Clin Immunol & Allergy, Los Angeles, CA 90095 USA
[2] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA
[3] Univ Iowa, Interdisciplinary Grad Program Immunol, Iowa City, IA 52242 USA
关键词
D O I
10.1128/MCB.18.9.5414
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
T lymphocytes undergo apoptosis in response to a variety of stimuli, including exposure to UV radiation and gamma-irradiation. Wile the mechanism by which stress stimuli induce apoptosis is not well understood, we have previously show that the induction of Fas ligand (FasL) gene expression by environmental stress stimuli is dependent on c-Jun N-terminal kinase (JNK) activation. Using inducible dominant-active (DA) JNK kinase kinase (MEKK1) expression in Jurkat cells, we map a specific MEKK1-regulated response clement to positions -338 to -316 of the Fas ligand (FasL) promoter. Mutation of that response element abrogated MEKK1-mediated Fast promoter activation and interfered in stress-induced activation of that promoter. Using electrophoretic mobility shift assays, we demonstrate that activator protein 1 (AP-1) binding proteins, namely, activating transcription factor 2 (ATF2) and c-Jun, bind to the MEKK1 response element. Transient transfection of interfering c-Jun and ATF2 mutants, which lack the consensus JNK phosphorylation sites, abrogated the transcriptional activation of the Fast promoter, demonstrating the involvement of these transcription factors in the regulation of the Fast promoter. Taken together, our data indicate that MEKK1 and transcription factors regulated by the JNK pathway play a role in committing lymphocytes to undergo apoptosis by inducing Fast expression,ia a novel response element in the promoter of that gene.
引用
收藏
页码:5414 / 5424
页数:11
相关论文
共 59 条
[11]   JNK1 - A PROTEIN-KINASE STIMULATED BY UV-LIGHT AND HA-RAS THAT BINDS AND PHOSPHORYLATES THE C-JUN ACTIVATION DOMAIN [J].
DERIJARD, B ;
HIBI, M ;
WU, IH ;
BARRETT, T ;
SU, B ;
DENG, TL ;
KARIN, M ;
DAVIS, RJ .
CELL, 1994, 76 (06) :1025-1037
[12]   Sequential activation of ICE-like and CPP32-like proteases during Fas-mediated apoptosis [J].
Enari, M ;
Talanian, RV ;
Wong, WW ;
Nagata, S .
NATURE, 1996, 380 (6576) :723-726
[13]  
Faris M, 1998, J IMMUNOL, V160, P134
[14]   Regulation of interleukin-2 transcription by inducible stable expression of dominant negative and dominant active mitogen-activated protein kinase kinase kinase in Jurkat T cells - Evidence for the importance of Ras in a pathway that is controlled by dual receptor stimulation [J].
Faris, M ;
Kokot, N ;
Lee, L ;
Nel, AE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (44) :27366-27373
[15]   REGULATION OF INTERLEUKIN-2 GENE ENHANCER ACTIVITY BY THE T-CELL ACCESSORY MOLECULE CD28 [J].
FRASER, JD ;
IRVING, BA ;
CRABTREE, GR ;
WEISS, A .
SCIENCE, 1991, 251 (4991) :313-316
[16]   Apoptosis meets signal transduction: Elimination of a BAD influence [J].
Gajewski, TF ;
Thompson, CB .
CELL, 1996, 87 (04) :589-592
[17]   Mitogen-activated protein kinase-mediated Fas apoptotic signaling pathway [J].
Goillot, E ;
Raingeaud, J ;
Ranger, A ;
Tepper, RI ;
Davis, RJ ;
Harlow, E ;
Sanchez, I .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (07) :3302-3307
[18]   TRANSCRIPTIONAL ACTIVATION BY TETRACYCLINES IN MAMMALIAN-CELLS [J].
GOSSEN, M ;
FREUNDLIEB, S ;
BENDER, G ;
MULLER, G ;
HILLEN, W ;
BUJARD, H .
SCIENCE, 1995, 268 (5218) :1766-1769
[19]   TRANSCRIPTION FACTOR ATF2 REGULATION BY THE JNK SIGNAL-TRANSDUCTION PATHWAY [J].
GUPTA, S ;
CAMPBELL, D ;
DERIJARD, B ;
DAVIS, RJ .
SCIENCE, 1995, 267 (5196) :389-393
[20]   IONIZING-RADIATION ACTS ON CELLULAR MEMBRANES TO GENERATE CERAMIDE AND INITIATE APOPTOSIS [J].
HAIMOVITZFRIEDMAN, A ;
KAN, CC ;
EHLEITER, D ;
PERSAUD, RS ;
MCLOUGHLIN, M ;
FUKS, Z ;
KOLESNICK, RN .
JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 180 (02) :525-535