0 5 Human human JJ 6 11 tumor tumor NN 12 20 necrosis necrosis NN 21 27 factor factor NN 28 33 alpha alpha NN 34 38 gene gene NN 39 49 regulation regulation NN 50 52 in in IN 53 60 phorbol phorbol NN 61 66 ester ester NN 67 77 stimulated stimulate VBD 78 79 T t NN 80 83 and and CC 84 85 B B NNP 86 90 cell cell NN 91 96 lines line NNS 96 97 . . . 99 102 The the DT 103 110 minimal minimal JJ 111 117 region region NN 118 120 of of IN 121 124 the the DT 125 130 human human JJ 131 136 tumor tumor NN 137 145 necrosis necrosis NN 146 152 factor factor NN 153 158 alpha alpha NN 159 160 ( ( ( 160 169 TNF-alpha TNF-alpha NNP 169 170 ) ) ) 171 175 gene gene NN 176 184 promoter promoter NN 185 194 necessary necessary JJ 195 198 for for IN 199 202 its its PRP$ 203 218 transcriptional transcriptional JJ 219 228 induction induction NN 229 231 by by IN 232 239 phorbol phorbol NN 240 246 esters ester NNS 247 248 ( ( ( 248 251 PMA PMA NNP 251 252 ) ) ) 253 255 in in IN 256 261 human human JJ 262 263 T t NN 264 267 and and CC 268 269 B B NNP 270 280 lymphocyte lymphocyte NN 281 285 cell cell NN 286 291 lines line NNS 292 295 has have VBZ 296 300 been be VBN 301 310 localized localized JJ 311 318 between between IN 319 322 -52 -52 CD 323 326 and and CC 327 330 +89 +89 CD 331 342 nucleotides nucleotide NNS 343 344 ( ( ( 344 346 nt nt NN 346 347 ) ) ) 348 356 relative relative JJ 357 359 to to TO 360 363 the the DT 364 368 gene gene NN 368 370 ’s 's POS 371 386 transcriptional transcriptional JJ 387 392 start start NN 393 397 site site NN 397 398 . . . 399 409 Comparison comparison NN 410 412 of of IN 413 418 these these DT 419 428 sequences sequence NNS 429 431 to to TO 432 437 those those DT 438 446 required require VBN 447 449 to to TO 450 457 mediate mediate VB 458 463 virus virus NN 464 466 or or CC 467 485 lipopolysaccharide lipopolysaccharide NN 486 487 ( ( ( 487 490 LPS LPS NNP 490 491 ) ) ) 492 501 induction induction NN 502 504 of of IN 505 508 the the DT 509 513 gene gene NN 514 520 reveal reveal VBP 521 532 significant significant JJ 533 544 differences difference NNS 544 545 , , , 546 549 and and CC 550 554 thus thus RB 554 555 , , , 556 559 the the DT 560 568 sequence sequence NN 569 581 requirements requirement NNS 582 585 for for IN 586 589 PMA PMA NNP 590 599 induction induction NN 600 603 are be VBP 604 612 distinct distinct JJ 613 617 from from IN 618 623 those those DT 624 628 that that WDT 629 636 mediate mediate VBP 637 646 induction induction NN 647 649 by by IN 650 655 virus virus NN 656 658 or or CC 659 662 LPS lps NN 662 663 . . . 664 672 Although although IN 673 678 three three CD 679 684 sites site NNS 685 687 in in IN 688 691 the the DT 692 701 TNF-alpha TNF-alpha NNP 702 710 promoter promoter NN 711 712 ( ( ( 712 717 kappa kappa NN 718 719 1 1 CD 719 720 , , , 721 726 kappa kappa NN 727 728 2 2 CD 728 729 , , , 730 733 and and CC 734 739 kappa kappa NN 740 741 3 3 CD 741 742 ) ) ) 743 755 specifically specifically RB 756 760 bind bind VBP 761 764 the the DT 765 778 transcription transcription NN 779 785 factor factor NN 786 794 NF-kappa NF-kappa NNP 795 796 B B NNP 797 799 in in IN 800 808 lymphoid lymphoid JJ 809 816 nuclear nuclear JJ 817 825 extracts extract NNS 825 826 , , , 827 836 TNF-alpha TNF-alpha NNP 837 841 mRNA mRNA NNP 842 851 induction induction NN 852 854 by by IN 855 858 PMA PMA NNP 859 863 does do VBZ 864 867 not not RB 868 877 correlate correlate VB 878 882 with with IN 883 891 NF-kappa NF-kappa NNP 892 893 B B NNP 894 901 binding binding NN 902 912 activities activity NNS 913 922 displayed display VBN 923 925 by by IN 926 935 different different JJ 936 937 T t NN 938 941 and and CC 942 943 B B NNP 944 948 cell cell NN 949 954 lines line NNS 954 955 . . . 956 964 Moreover moreover RB 964 965 , , , 966 971 kappa kappa NN 972 979 1-kappa 1-kappa NN 980 981 3 3 CD 982 985 can can MD 986 990 each each DT 991 993 be be VB 994 1001 deleted delete VBN 1002 1006 from from IN 1007 1010 the the DT 1011 1020 TNF-alpha TNF-alpha NNP 1021 1029 promoter promoter NN 1030 1034 with with IN 1035 1041 little little JJ 1042 1048 effect effect NN 1049 1051 on on IN 1052 1055 the the DT 1056 1060 gene gene NN 1060 1062 ’s 's POS 1063 1075 inducibility inducibility NN 1076 1078 by by IN 1079 1082 PMA PMA NNP 1082 1083 . . . 1084 1093 Therefore therefore RB 1093 1094 , , , 1095 1104 TNF-alpha TNF-alpha NNP 1105 1109 mRNA mRNA NNP 1110 1119 induction induction NN 1120 1122 by by IN 1123 1126 PMA PMA NNP 1126 1127 , , , 1128 1132 like like IN 1133 1136 its its PRP$ 1137 1146 induction induction NN 1147 1149 by by IN 1150 1155 virus virus NN 1156 1159 and and CC 1160 1163 LPS LPS NNP 1163 1164 , , , 1165 1167 is be VBZ 1168 1171 not not RB 1172 1181 primarily primarily RB 1182 1190 mediated mediate VBN 1191 1193 by by IN 1194 1202 NF-kappa NF-kappa NNP 1203 1204 B B NNP 1204 1205 , , , 1206 1209 but but CC 1210 1216 rather rather RB 1217 1219 is be VBZ 1220 1228 mediated mediate VBN 1229 1236 through through IN 1237 1242 other other JJ 1243 1252 sequences sequence NNS 1253 1256 and and CC 1257 1264 protein protein NN 1265 1272 factors factor NNS 1272 1273 . . . 1274 1286 Surprisingly surprisingly RB 1286 1287 , , , 1288 1297 multimers multimer NNS 1298 1300 of of IN 1301 1306 kappa kappa NN 1307 1314 1-kappa 1-kappa NN 1315 1316 3 3 CD 1317 1320 can can MD 1321 1327 confer confer VB 1328 1331 PMA PMA NNP 1332 1344 inducibility inducibility NN 1345 1347 on on IN 1348 1349 a a DT 1350 1362 heterologous heterologous JJ 1363 1371 promoter promoter NN 1372 1374 in in IN 1375 1376 a a DT 1377 1378 B B NNP 1379 1380 ( ( ( 1380 1384 Raji Raji NNP 1384 1385 ) ) ) 1385 1386 , , , 1387 1390 but but CC 1391 1394 not not RB 1395 1396 a a DT 1397 1398 T t NN 1399 1400 ( ( ( 1400 1405 HUT78 HUT78 NNP 1405 1406 ) ) ) 1407 1411 cell cell NN 1412 1416 line line NN 1416 1417 . . . 1418 1425 However however RB 1426 1430 they they PRP 1431 1434 are be VBP 1435 1438 not not RB 1439 1449 functional functional JJ 1450 1452 on on IN 1453 1454 a a DT 1455 1464 truncated truncate VBN 1465 1474 TNF-alpha TNF-alpha NNP 1475 1483 promoter promoter NN 1483 1484 , , , 1485 1495 indicating indicate VBG 1496 1500 that that IN 1501 1509 promoter promoter NN 1510 1517 context context NN 1518 1521 and and CC 1522 1526 cell cell NN 1527 1531 type type NN 1532 1543 specificity specificity NN 1544 1553 influence influence VBP 1554 1557 the the DT 1558 1561 PMA PMA NNP 1562 1571 inducible inducible JJ 1572 1580 function function NN 1581 1583 of of IN 1584 1589 these these DT 1590 1598 NF-kappa NF-kappa NNP 1599 1600 B B NNP 1601 1608 binding binding NN 1609 1614 sites site NNS 1614 1615 . . .