0 3 The the DT 4 15 lymphotoxin lymphotoxin NN 16 24 promoter promoter NN 25 27 is be VBZ 28 38 stimulated stimulate VBN 39 41 by by IN 42 48 HTLV-I HTLV-I NNP 49 52 tax tax NN 53 63 activation activation NN 64 66 of of IN 67 75 NF-kappa NF-kappa NNP 76 77 B B NNP 78 80 in in IN 81 86 human human JJ 87 93 T-cell t-cell NN 94 99 lines line NNS 99 100 . . . 102 105 The the DT 106 112 HTLV-I HTLV-I NNP 113 128 transcriptional transcriptional JJ 129 138 activator activator NN 139 142 tax tax NN 143 146 was be VBD 147 151 used use VBN 152 154 to to TO 155 159 gain gain VB 160 167 insight insight NN 168 172 into into IN 173 176 the the DT 177 186 mechanism mechanism NN 187 189 of of IN 190 201 lymphotoxin lymphotoxin NN 202 203 ( ( ( 203 205 LT LT NNP 205 206 ; ; : 207 215 TNF-beta TNF-beta NNP 215 216 ) ) ) 217 221 gene gene NN 222 231 induction induction NN 231 232 . . . 233 247 Tax-expressing tax-expressing JJ 248 252 cell cell NN 253 258 lines line NNS 259 266 produce produce VBP 267 269 LT lt NN 270 278 biologic biologic JJ 279 287 activity activity NN 287 288 . . . 289 291 An an DT 292 294 LT LT NNP 295 303 promoter promoter NN 304 305 ( ( ( 305 311 LT-293 LT-293 NNP 311 312 ) ) ) 313 316 CAT CAT NNP 317 326 construct construct NN 327 331 that that WDT 332 341 contained contain VBD 342 344 an an DT 345 353 NF-kappa NF-kappa NNP 354 355 B B NNP 356 360 site site NN 361 364 was be VBD 365 371 active active JJ 372 374 in in IN 375 378 the the DT 379 391 LT-producing lt-producing JJ 392 401 C81-66-45 C81-66-45 NNP 402 406 cell cell NN 407 411 line line NN 411 412 , , , 413 418 which which WDT 419 427 contains contain VBZ 428 437 defective defective JJ 438 444 HTLV-I HTLV-I NNP 445 448 but but CC 449 458 expresses express VBZ 459 462 tax tax NN 462 463 . . . 464 467 The the DT 468 479 observation observation NN 480 484 that that IN 485 486 a a DT 487 494 mutated mutate VBN 495 503 LT-kappa LT-kappa NNP 504 505 B B NNP 506 515 construct construct NN 516 517 ( ( ( 517 523 M1-CAT M1-CAT NNP 523 524 ) ) ) 525 528 was be VBD 529 537 inactive inactive JJ 538 540 in in IN 541 550 C81-66-45 C81-66-45 NNP 550 551 , , , 552 561 confirmed confirm VBD 562 565 the the DT 566 576 importance importance NN 577 579 of of IN 580 588 NF-kappa NF-kappa NNP 589 590 B B NNP 591 593 in in IN 594 596 LT LT NNP 597 601 gene gene NN 602 612 expression expression NN 612 613 . . . 614 617 Tax Tax NNP 618 621 was be VBD 622 633 transfected transfecte VBN 634 638 into into IN 639 654 HTLV-I-negative htlv-i-negative JJ 655 660 human human JJ 661 667 T-cell t-cell NN 668 673 lines line NNS 673 674 . . . 675 681 Jurkat Jurkat NNP 682 683 T t NN 684 689 cells cell NNS 690 696 stably stably RB 697 707 expressing express VBG 708 711 tax tax NN 712 721 contained contain VBD 722 730 elevated elevated JJ 731 737 levels level NNS 738 740 of of IN 741 749 NF-kappa NF-kappa NNP 750 751 B B NNP 752 756 that that WDT 757 765 directly directly RB 766 771 bound bind VBD 772 774 to to TO 775 778 the the DT 779 787 LT-kappa LT-kappa NNP 788 789 B B NNP 790 794 site site NN 794 795 . . . 796 799 Tax Tax NNP 800 814 co-transfected co-transfecte VBN 815 819 with with IN 820 828 reporter reporter NN 829 839 constructs construct NNS 840 844 into into IN 845 851 Jurkat Jurkat NNP 852 857 cells cell NNS 858 867 maximally maximally RB 868 877 activated activate VBD 878 892 HTLV-I-LTR-CAT HTLV-I-LTR-CAT NNP 893 896 and and CC 897 902 kappa kappa NN 903 912 B-fos-CAT B-fos-CAT NNP 913 916 and and CC 917 921 also also RB 922 931 activated activate VBD 932 938 LT-293 lt-293 NN 939 941 to to TO 942 943 a a DT 944 950 lesser less JJR 951 957 extent extent NN 957 958 . . . 959 961 In in IN 962 964 JM JM NNP 965 966 T t NN 967 972 cells cell NNS 972 973 , , , 974 977 tax tax NN 978 985 induced induce VBD 986 992 LT-293 lt-293 NN 993 1001 activity activity NN 1002 1004 by by IN 1005 1009 two- two- CD 1010 1012 to to TO 1013 1022 four-fold four-fold RB 1022 1023 , , , 1024 1030 though though IN 1031 1036 there there EX 1037 1040 was be VBD 1041 1043 no no DT 1044 1053 induction induction NN 1054 1056 of of IN 1057 1063 M1-CAT M1-CAT NNP 1063 1064 . . . 1065 1068 The the DT 1069 1077 increase increase NN 1078 1080 in in IN 1081 1087 LT-293 LT-293 NNP 1088 1091 CAT CAT NNP 1092 1100 activity activity NN 1101 1109 mirrored mirror VBD 1110 1113 the the DT 1114 1122 increase increase NN 1123 1125 in in IN 1126 1128 LT LT NNP 1129 1137 biologic biologic JJ 1138 1146 activity activity NN 1147 1151 seen see VBN 1152 1157 under under IN 1158 1163 these these DT 1164 1174 conditions condition NNS 1174 1175 . . . 1176 1181 These these DT 1182 1189 studies study NNS 1189 1190 , , , 1191 1194 the the DT 1195 1200 first first JJ 1201 1203 to to TO 1204 1215 demonstrate demonstrate VB 1216 1225 induction induction NN 1226 1228 of of IN 1229 1231 LT LT NNP 1232 1240 promoter promoter NN 1241 1249 activity activity NN 1250 1254 over over IN 1255 1260 basal basal JJ 1261 1267 levels level NNS 1267 1268 , , , 1269 1277 indicate indicate VBP 1278 1282 that that IN 1283 1289 HTLV-I HTLV-I NNP 1290 1293 tax tax NN 1294 1300 causes cause VBZ 1301 1310 low-level low-level JJ 1311 1321 activation activation NN 1322 1324 of of IN 1325 1329 both both CC 1330 1340 endogenous endogenous JJ 1341 1343 LT lt NN 1344 1347 and and CC 1348 1351 the the DT 1352 1354 LT LT NNP 1355 1363 promoter promoter NN 1363 1364 , , , 1365 1367 at at IN 1368 1373 least least JJS 1374 1376 in in IN 1377 1381 part part NN 1382 1389 through through IN 1390 1400 activation activation NN 1401 1403 of of IN 1404 1412 NF-kappa NF-kappa NNP 1413 1414 B B NNP 1414 1415 . . .