0 15 Transactivation Transactivation NNP 16 18 of of IN 19 22 the the DT 23 41 interleukin-1alpha interleukin-1alpha NN 42 50 promoter promoter NN 51 53 by by IN 54 59 human human JJ 60 66 T-cell t-cell NN 67 75 leukemia leukemia NN 76 81 virus virus NN 82 86 type type NN 87 88 I i CD 89 92 and and CC 93 97 type type NN 98 100 II ii CD 101 104 Tax Tax NNP 105 113 proteins protein NNS 113 114 . . . 116 121 Human human JJ 122 128 T-cell T-cell NNP 129 137 leukemia leukemia NN 138 143 virus virus NN 144 148 type type NN 149 150 I i CD 151 152 ( ( ( 152 168 HTLV-I)-infected htlv-i)-infected JJ 169 175 T-cell t-cell NN 176 181 lines line NNS 182 196 constitutively constitutively RB 197 204 produce produce VBP 205 209 high high JJ 210 216 levels level NNS 217 219 of of IN 220 238 interleukin-1alpha interleukin-1alpha NN 239 240 ( ( ( 240 249 IL-1alpha IL-1alpha NNP 249 250 ) ) ) 250 251 . . . 252 254 To to TO 255 262 analyze analyze VB 263 266 the the DT 267 277 mechanisms mechanism NNS 278 282 that that WDT 283 287 lead lead VBP 288 290 to to TO 291 294 the the DT 295 305 expression expression NN 306 308 of of IN 309 318 IL-1alpha IL-1alpha NNP 319 321 in in IN 322 337 HTLV-I-infected htlv-i-infected JJ 338 342 cell cell NN 343 348 lines line NNS 348 349 , , , 350 352 we we PRP 353 360 studied study VBD 361 371 regulatory regulatory JJ 372 379 regions region NNS 380 382 of of IN 383 386 the the DT 387 392 human human JJ 393 402 IL-1alpha IL-1alpha NNP 403 411 promoter promoter NN 412 420 involved involve VBN 421 423 in in IN 424 434 activation activation NN 435 437 of of IN 438 441 the the DT 442 451 IL-1alpha IL-1alpha NNP 452 456 gene gene NN 456 457 . . . 458 467 IL-1alpha IL-1alpha NNP 468 476 promoter promoter NN 477 487 constructs construct NNS 488 493 drive drive VBP 494 507 transcription transcription NN 508 510 of of IN 511 514 the the DT 515 530 chloramphenicol chloramphenicol NN 531 548 acetyltransferase acetyltransferase NN 549 550 ( ( ( 550 553 CAT CAT NNP 553 554 ) ) ) 555 563 reporter reporter NN 564 568 gene gene NN 569 571 in in IN 572 587 HTLV-I-positive htlv-i-positive JJ 588 592 MT-2 mt-2 NN 593 598 cells cell NNS 598 599 , , , 600 605 which which WDT 606 620 constitutively constitutively RB 621 628 produce produce VBP 629 638 IL-1alpha IL-1alpha NNP 638 639 . . . 640 642 In in IN 643 644 a a DT 645 659 cotransfection cotransfection NN 660 665 assay assay NN 665 666 , , , 667 670 the the DT 671 674 Tax Tax NNP 675 682 protein protein NN 683 685 of of IN 686 690 both both CC 691 697 HTLV-I HTLV-I NNP 698 701 and and CC 702 709 HTLV-II HTLV-II NNP 710 722 specifically specifically RB 723 732 activated activate VBD 733 746 transcription transcription NN 747 751 from from IN 752 755 the the DT 756 765 IL-1alpha IL-1alpha NNP 766 774 promoter promoter NN 775 777 in in IN 778 780 an an DT 781 791 uninfected uninfected JJ 792 798 Jurkat Jurkat NNP 799 803 cell cell NN 804 808 line line NN 808 809 . . . 810 811 A a DT 812 818 mutant mutant JJ 819 822 Tax tax NN 823 830 protein protein NN 831 840 deficient deficient JJ 841 843 in in IN 844 859 transactivation transactivation NN 860 862 of of IN 863 868 genes gene NNS 869 871 by by IN 872 875 the the DT 876 883 nuclear nuclear JJ 884 890 factor factor NN 891 892 ( ( ( 892 902 NF)-kappaB NF)-kappaB NNP 903 910 pathway pathway NN 911 914 was be VBD 915 921 unable unable JJ 922 924 to to TO 925 931 induce induce VB 932 947 transcriptional transcriptional JJ 948 956 activity activity NN 957 959 of of IN 960 969 IL-1alpha IL-1alpha NNP 970 982 promoter-CAT promoter-cat NN 983 993 constructs construct NNS 993 994 , , , 995 998 but but CC 999 1002 was be VBD 1003 1010 rescued rescue VBN 1011 1013 by by IN 1014 1023 exogenous exogenous JJ 1024 1033 provision provision NN 1034 1036 of of IN 1037 1044 p65/p50 p65/p50 NN 1045 1054 NF-kappaB nf-kappab NN 1054 1055 . . . 1056 1058 We we PRP 1059 1064 found find VBD 1065 1069 that that IN 1070 1073 two two CD 1074 1083 IL-1alpha IL-1alpha NNP 1084 1095 kappaB-like kappab-like JJ 1096 1101 sites site NNS 1102 1103 ( ( ( 1103 1112 positions position NNS 1113 1119 -1,065 -1,065 CD 1120 1122 to to TO 1123 1129 -1,056 -1,056 CD 1130 1133 and and CC 1134 1138 +646 +646 CD 1139 1141 to to TO 1142 1146 +655 +655 CD 1146 1147 ) ) ) 1148 1160 specifically specifically RB 1161 1167 formed form VBD 1168 1169 a a DT 1170 1177 complex complex NN 1178 1182 with with IN 1183 1203 NF-kappaB-containing nf-kappab-containing JJ 1204 1211 nuclear nuclear JJ 1212 1219 extract extract NN 1220 1224 from from IN 1225 1229 MT-2 mt-2 NN 1230 1235 cells cell NNS 1236 1239 and and CC 1240 1244 that that IN 1245 1254 NF-kappaB NF-kappaB NNP 1255 1260 bound bind VBD 1261 1265 with with IN 1266 1272 higher high JJR 1273 1281 affinity affinity NN 1282 1284 to to TO 1285 1288 the the DT 1289 1290 3 3 CD 1290 1291 ’ ' SYM 1292 1301 NF-kappaB NF-kappaB NNP 1302 1309 binding binding NN 1310 1314 site site NN 1315 1319 than than IN 1320 1322 to to TO 1323 1326 the the DT 1327 1328 5 5 CD 1328 1329 ’ ' SYM 1330 1339 NF-kappaB NF-kappaB NNP 1340 1344 site site NN 1344 1345 . . . 1346 1354 Moreover moreover RB 1354 1355 , , , 1356 1364 deletion deletion NN 1365 1367 of of IN 1368 1374 either either CC 1375 1376 5 5 CD 1376 1377 ’ ' SYM 1378 1380 or or CC 1381 1382 3 3 CD 1382 1383 ’ ' SYM 1384 1393 NF-kappaB NF-kappaB NNP 1394 1399 sites site NNS 1400 1407 reduced reduce VBD 1408 1417 IL-1alpha IL-1alpha NNP 1418 1426 promoter promoter NN 1427 1435 activity activity NN 1436 1438 in in IN 1439 1443 MT-2 mt-2 NN 1444 1449 cells cell NNS 1450 1453 and and CC 1454 1469 transactivation transactivation NN 1470 1472 of of IN 1473 1476 the the DT 1477 1486 IL-1alpha IL-1alpha NNP 1487 1495 promoter promoter NN 1496 1498 by by IN 1499 1508 exogenous exogenous JJ 1509 1518 NF-kappaB NF-kappaB NNP 1519 1522 and and CC 1523 1526 Tax Tax NNP 1527 1529 in in IN 1530 1536 Jurkat Jurkat NNP 1537 1542 cells cell NNS 1542 1543 . . . 1544 1549 These these DT 1550 1554 data datum NNS 1555 1562 suggest suggest VBP 1563 1564 a a DT 1565 1572 general general JJ 1573 1577 role role NN 1578 1581 for for IN 1582 1585 Tax Tax NNP 1586 1595 induction induction NN 1596 1598 of of IN 1599 1608 IL-1alpha IL-1alpha NNP 1609 1613 gene gene NN 1614 1627 transcription transcription NN 1628 1630 by by IN 1631 1634 the the DT 1635 1644 NF-kappaB NF-kappaB NNP 1645 1652 pathway pathway NN 1652 1653 . . . 1654 1664 Expression expression NN 1665 1667 of of IN 1668 1677 IL-1alpha IL-1alpha NNP 1678 1680 by by IN 1681 1687 HTLV-I HTLV-I NNP 1688 1700 productively productively RB 1701 1709 infected infected JJ 1710 1715 cells cell NNS 1716 1719 may may MD 1720 1722 be be VB 1723 1732 important important JJ 1733 1735 in in IN 1736 1739 the the DT 1740 1753 hypercalcemia hypercalcemia NN 1753 1754 , , , 1755 1765 osteolytic osteolytic JJ 1766 1770 bone bone NN 1771 1778 lesions lesion NNS 1778 1779 , , , 1780 1792 neutrophilia neutrophilia NN 1792 1793 , , , 1794 1803 elevation elevation NN 1804 1806 of of IN 1807 1817 C-reactive c-reactive JJ 1818 1825 protein protein NN 1825 1826 , , , 1827 1830 and and CC 1831 1836 fever fever NN 1837 1847 frequently frequently RB 1848 1852 seen see VBN 1853 1855 in in IN 1856 1864 patients patient NNS 1865 1869 with with IN 1870 1884 HTLV-I-induced htlv-i-induced JJ 1885 1890 adult adult JJ 1891 1897 T-cell t-cell NN 1898 1915 leukemia/lymphoma leukemia/lymphoma NN 1915 1916 . . .