THE IMMUNOSUPPRESSIVES FK-506 AND CYCLOSPORINE-A INHIBIT THE GENERATION OF PROTEIN FACTORS BINDING TO THE 2 PURINE BOXES OF THE INTERLEUKIN-2 ENHANCER

被引:91
作者
BRABLETZ, T [1 ]
PIETROWSKI, I [1 ]
SERFLING, E [1 ]
机构
[1] UNIV WURZBURG,INST VIROL & IMMUNBIOL,VERSBACHER STR 7,W-8700 WURZBURG,GERMANY
关键词
D O I
10.1093/nar/19.1.61
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
Like Cyclosporin A (CsA), the macrolide FK 506 is a potent immunosuppressive that inhibits early steps of T cell activation, including the synthesis of Interleukin 2 (II-2) and numerous other lymphokines. The block of II-2 synthesis occurs at the transcriptional level. At concentrations that block T cell activation, FK 506 and CsA inhibit the proto-enhancer activity of Purine boxes of the II-2 promoter and the generation of lymphocyte-specific factors binding to the Purine boxes. Under the same conditions, the DNA binding of other II-2 enhancer factors remains unaffected by both compounds. These results support the view that FK 506 and CsA, which both inhibit the activity of peptidylprolyl cis/trans isomerases, suppress T cell activation by a similar, if not identical mechanism.
引用
收藏
页码:61 / 67
页数:7
相关论文
共 23 条
[1]   PHORBOL ESTER INDUCIBLE GENES CONTAIN A COMMON CIS ELEMENT RECOGNIZED BY A TPA-MODULATED TRANS-ACTING FACTOR [J].
ANGEL, P ;
IMAGAWA, M ;
CHIU, R ;
STEIN, B ;
IMBRA, RJ ;
RAHMSDORF, HJ ;
JONAT, C ;
HERRLICH, P ;
KARIN, M .
CELL, 1987, 49 (06) :729-739
[2]  
BRIEGEL K, 1990, UNPUB
[3]  
EMMEL EA, 1989, SCIENCE, V226, P1439
[4]   CYCLOPHILIN AND PEPTIDYL-PROLYL CIS-TRANS ISOMERASE ARE PROBABLY IDENTICAL PROTEINS [J].
FISCHER, G ;
WITTMANNLIEBOLD, B ;
LANG, K ;
KIEFHABER, T ;
SCHMID, FX .
NATURE, 1989, 337 (6206) :476-478
[5]  
KAHAN BD, 1989, NEW ENGL J MED, V321, P1725
[6]   CYCLOSPORIN-A INHIBITS T-CELL GROWTH-FACTOR GENE-EXPRESSION AT THE LEVEL OF MESSENGER-RNA TRANSCRIPTION [J].
KRONKE, M ;
LEONARD, WJ ;
DEPPER, JM ;
ARYA, SK ;
WONGSTAAL, F ;
GALLO, RC ;
WALDMANN, TA ;
GREENE, WC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (16) :5214-5218
[7]   CAT CONSTRUCTIONS WITH MULTIPLE UNIQUE RESTRICTION SITES FOR THE FUNCTIONAL-ANALYSIS OF EUKARYOTIC PROMOTERS AND REGULATORY ELEMENTS [J].
LUCKOW, B ;
SCHUTZ, G .
NUCLEIC ACIDS RESEARCH, 1987, 15 (13) :5490-5490
[8]   COMPLEMENTARY-DNA ENCODING THE HUMAN T-CELL FK506-BINDING PROTEIN, A PEPTIDYLPROLYL CIS-TRANS ISOMERASE DISTINCT FROM CYCLOPHILIN [J].
MAKI, N ;
SEKIGUCHI, F ;
NISHIMAKI, J ;
MIWA, K ;
HAYANO, T ;
TAKAHASHI, N ;
SUZUKI, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (14) :5440-5443
[9]  
RADLER-POHL A, 1990, New Biologist, V2, P566
[10]   CYCLOSPORINE-A SUPPRESSES THE EXPRESSION OF THE INTERLEUKIN-2 GENE BY INHIBITING THE BINDING OF LYMPHOCYTE-SPECIFIC FACTORS TO THE IL-2 ENHANCER [J].
RANDAK, C ;
BRABLETZ, T ;
HERGENROTHER, M ;
SOBOTTA, I ;
SERFLING, E .
EMBO JOURNAL, 1990, 9 (08) :2529-2536