0 10 Regulation Regulation NNP 11 13 of of IN 14 18 CD95 CD95 NNP 19 20 ( ( ( 20 23 Fas Fas NNP 23 24 ) ) ) 25 31 ligand ligand NN 32 42 expression expression NN 43 45 by by IN 46 58 TCR-mediated tcr-mediated JJ 59 68 signaling signaling NN 69 75 events event NNS 75 76 . . . 78 89 Stimulation stimulation NN 90 92 of of IN 93 99 mature mature JJ 100 110 peripheral peripheral JJ 111 112 T t NN 113 118 cells cell NNS 119 121 by by IN 122 125 TCR TCR NNP 126 136 engagement engagement NN 137 144 results result VBZ 145 147 in in IN 148 158 activation activation NN 159 161 of of IN 162 169 signals signal NNS 170 174 that that WDT 175 180 drive drive VBP 181 190 induction induction NN 191 193 of of IN 194 202 cytokine cytokine NN 203 207 gene gene NN 208 218 expression expression NN 219 222 and and CC 223 229 clonal clonal JJ 230 239 expansion expansion NN 239 240 . . . 241 248 However however RB 248 249 , , , 250 255 under under IN 256 260 some some DT 261 271 conditions condition NNS 271 272 , , , 273 283 engagement engagement NN 284 286 of of IN 287 290 the the DT 291 294 TCR TCR NNP 295 300 leads lead VBZ 301 308 instead instead RB 309 311 to to TO 312 321 apoptosis apoptosis NN 321 322 . . . 323 329 Recent recent JJ 330 337 studies study NNS 338 349 demonstrate demonstrate VBP 350 354 that that IN 355 369 TCR-stimulated tcr-stimulated JJ 370 379 apoptosis apoptosis NN 380 388 requires require VBZ 389 399 expression expression NN 400 402 of of IN 403 407 CD95 cd95 NN 408 414 ligand ligand NN 415 417 on on IN 418 427 activated activate VBN 428 429 T t NN 430 435 cells cell NNS 436 444 followed follow VBN 445 447 by by IN 448 450 an an DT 451 462 interaction interaction NN 463 470 between between IN 471 475 CD95 CD95 NNP 476 482 ligand ligand NN 483 486 and and CC 487 490 the the DT 491 495 CD95 CD95 NNP 496 504 receptor receptor NN 505 509 also also RB 510 519 expressed express VBN 520 522 on on IN 523 527 this this DT 528 538 population population NN 538 539 . . . 540 543 The the DT 544 555 experiments experiment NNS 556 564 reported report VBN 565 567 in in IN 568 572 this this DT 573 578 study study NN 579 583 were be VBD 584 592 designed design VBN 593 595 to to TO 596 603 address address VB 604 607 the the DT 608 617 signaling signaling NN 618 624 events event NNS 625 634 triggered trigger VBN 635 637 by by IN 638 641 TCR TCR NNP 642 652 engagement engagement NN 653 657 that that WDT 658 661 are be VBP 662 671 important important JJ 672 675 for for IN 676 686 regulating regulate VBG 687 691 CD95 cd95 NN 692 698 ligand ligand NN 699 703 gene gene NN 704 714 expression expression NN 714 715 . . . 716 718 To to TO 719 727 approach approach VB 728 732 this this DT 732 733 , , , 734 736 we we PRP 737 746 generated generate VBD 747 748 a a DT 749 759 luciferase luciferase NN 760 768 reporter reporter NN 769 778 construct construct NN 779 789 containing contain VBG 790 798 elements element NNS 799 801 of of IN 802 805 the the DT 806 810 CD95 CD95 NNP 811 817 ligand ligand NN 818 826 promoter promoter NN 826 827 . . . 828 833 Using use VBG 834 835 a a DT 836 846 previously previously RB 847 856 described describe VBN 857 863 mutant mutant NN 864 866 of of IN 867 870 the the DT 871 877 Jurkat Jurkat NNP 878 879 T t NN 880 884 cell cell NN 885 889 line line NN 889 890 , , , 891 893 we we PRP 894 898 show show VBP 899 903 that that IN 904 912 proximal proximal JJ 913 922 signaling signaling NN 923 929 events event NNS 930 939 dependent dependent JJ 940 942 on on IN 943 946 the the DT 947 955 presence presence NN 956 958 of of IN 959 962 the the DT 963 967 CD45 CD45 NNP 968 976 tyrosine tyrosine NN 977 988 phosphatase phosphatase NN 989 992 are be VBP 993 1001 required require VBN 1002 1005 for for IN 1006 1020 TCR-stimulated tcr-stimulated JJ 1021 1025 CD95 cd95 NN 1026 1032 ligand ligand NN 1033 1043 expression expression NN 1043 1044 . . . 1045 1054 Transient transient JJ 1055 1067 transfection transfection NN 1068 1075 studies study NNS 1076 1087 demonstrate demonstrate VBP 1088 1095 further further RBR 1096 1100 that that IN 1101 1115 TCR-stimulated tcr-stimulated JJ 1116 1126 activation activation NN 1127 1129 of of IN 1130 1133 the the DT 1134 1137 Ras Ras NNPS 1138 1147 signaling signaling NN 1148 1155 pathway pathway NN 1156 1158 is be VBZ 1159 1167 required require VBN 1168 1171 for for IN 1172 1179 optimal optimal JJ 1180 1190 activation activation NN 1191 1193 of of IN 1194 1198 CD95 CD95 NNP 1199 1205 ligand ligand NN 1205 1206 . . . 1207 1211 Next next RB 1211 1212 , , , 1213 1215 in in IN 1216 1218 an an DT 1219 1225 effort effort NN 1226 1228 to to TO 1229 1238 determine determine VB 1239 1247 critical critical JJ 1248 1261 transcription transcription NN 1262 1269 factors factor NNS 1270 1274 that that WDT 1275 1283 regulate regulate VBP 1284 1288 CD95 CD95 NNP 1289 1295 ligand ligand NN 1296 1306 expression expression NN 1306 1307 , , , 1308 1310 we we PRP 1311 1322 demonstrate demonstrate VBP 1323 1324 a a DT 1325 1336 cyclosporin cyclosporin NN 1337 1348 A-sensitive a-sensitive JJ 1349 1356 nuclear nuclear JJ 1357 1366 factor-AT factor-at NN 1367 1375 response response NN 1376 1383 element element NN 1384 1386 in in IN 1387 1390 the the DT 1391 1399 promoter promoter NN 1400 1406 region region NN 1407 1409 of of IN 1410 1414 this this DT 1415 1419 gene gene NN 1420 1424 that that WDT 1425 1427 is be VBZ 1428 1436 critical critical JJ 1437 1440 for for IN 1441 1448 optimal optimal JJ 1449 1453 CD95 cd95 NN 1454 1460 ligand ligand NN 1461 1469 reporter reporter NN 1470 1478 activity activity NN 1479 1481 in in IN 1482 1492 stimulated stimulate VBN 1493 1494 T t NN 1495 1500 cells cell NNS 1500 1501 . . . 1502 1510 Together together RB 1510 1511 , , , 1512 1517 these these DT 1518 1525 studies study NNS 1526 1531 begin begin VBP 1532 1533 a a DT 1534 1544 dissection dissection NN 1545 1547 of of IN 1548 1551 the the DT 1552 1563 biochemical biochemical JJ 1564 1570 events event NNS 1571 1575 that that WDT 1576 1580 lead lead VBP 1581 1583 to to TO 1584 1594 expression expression NN 1595 1597 of of IN 1598 1602 CD95 CD95 NNP 1603 1609 ligand ligand NN 1609 1610 , , , 1611 1612 a a DT 1613 1621 required required JJ 1622 1626 step step NN 1627 1630 for for IN 1631 1642 TCR-induced tcr-induced JJ 1643 1652 apoptosis apoptosis NN 1652 1653 . . .