0 3 The the DT 4 16 Epstein-Barr epstein-barr JJ 17 22 virus virus NN 23 31 oncogene oncogene NN 32 39 product product NN 40 46 latent latent JJ 47 55 membrane membrane NN 56 63 protein protein NN 64 65 1 1 CD 66 73 engages engage VBZ 74 77 the the DT 78 83 tumor tumor NN 84 92 necrosis necrosis NN 93 99 factor factor NN 100 119 receptor-associated receptor-associated JJ 120 125 death death NN 126 132 domain domain NN 133 140 protein protein NN 141 143 to to TO 144 151 mediate mediate VB 152 153 B B NNP 154 164 lymphocyte lymphocyte NN 165 171 growth growth NN 172 186 transformation transformation NN 187 190 and and CC 191 199 activate activate VBP 200 209 NF-kappaB NF-kappaB NNP 209 210 . . . 212 215 The the DT 216 228 Epstein-Barr epstein-barr JJ 229 234 virus virus NN 235 241 latent latent JJ 242 250 membrane membrane NN 251 258 protein protein NN 259 260 1 1 CD 261 262 ( ( ( 262 266 LMP1 lmp1 NN 266 267 ) ) ) 268 270 is be VBZ 271 280 essential essential JJ 281 284 for for IN 285 288 the the DT 289 303 transformation transformation NN 304 306 of of IN 307 308 B B NNP 309 320 lymphocytes lymphocyte NNS 321 325 into into IN 326 340 lymphoblastoid lymphoblastoid JJ 341 345 cell cell NN 346 351 lines line NNS 351 352 . . . 353 361 Previous previous JJ 362 366 data datum NNS 367 370 are be VBP 371 381 consistent consistent JJ 382 386 with with IN 387 388 a a DT 389 394 model model NN 395 399 that that IN 400 404 LMP1 LMP1 NNP 405 407 is be VBZ 408 409 a a DT 410 424 constitutively constitutively RB 425 434 activated activate VBN 435 443 receptor receptor NN 444 448 that that WDT 449 459 transduces transduce VBZ 460 467 signals signal NNS 468 471 for for IN 472 486 transformation transformation NN 487 494 through through IN 495 498 its its PRP$ 499 516 carboxyl-terminal carboxyl-terminal JJ 517 528 cytoplasmic cytoplasmic JJ 529 533 tail tail NN 533 534 . . . 535 538 One one CD 539 553 transformation transformation NN 554 562 effector effector NN 563 567 site site NN 568 569 ( ( ( 569 573 TES1 TES1 NNP 573 574 ) ) ) 574 575 , , , 576 583 located located JJ 584 590 within within IN 591 594 the the DT 595 603 membrane membrane NN 604 612 proximal proximal JJ 613 615 45 45 CD 616 624 residues residue NNS 625 627 of of IN 628 631 the the DT 632 643 cytoplasmic cytoplasmic JJ 644 648 tail tail NN 648 649 , , , 650 664 constitutively constitutively RB 665 672 engages engage VBZ 673 678 tumor tumor NN 679 687 necrosis necrosis NN 688 694 factor factor NN 695 714 receptor-associated receptor-associated JJ 715 722 factors factor NNS 722 723 . . . 724 731 Signals signal NNS 732 736 from from IN 737 741 TES1 TES1 NNP 742 745 are be VBP 746 756 sufficient sufficient JJ 757 759 to to TO 760 765 drive drive VB 766 773 initial initial JJ 774 787 proliferation proliferation NN 788 790 of of IN 791 799 infected infected JJ 800 807 resting rest VBG 808 809 B b NN 810 821 lymphocytes lymphocyte NNS 821 822 , , , 823 826 but but CC 827 831 most most JJS 832 846 lymphoblastoid lymphoblastoid JJ 847 852 cells cell NNS 853 861 infected infect VBN 862 866 with with IN 867 868 a a DT 869 874 virus virus NN 875 879 that that WDT 880 884 does do VBZ 885 888 not not RB 889 896 express express VB 897 900 the the DT 901 904 155 155 CD 905 913 residues residue NNS 914 920 beyond beyond IN 921 925 TES1 TES1 NNP 926 930 fail fail VBP 931 933 to to TO 934 938 grow grow VB 939 941 as as IN 942 951 long-term long-term JJ 952 956 cell cell NN 957 962 lines line NNS 962 963 . . . 964 966 We we PRP 967 970 now now RB 971 975 find find VBP 976 980 that that IN 981 989 mutating mutate VBG 990 993 two two CD 994 1003 tyrosines tyrosine NNS 1004 1006 to to TO 1007 1009 an an DT 1010 1020 isoleucine isoleucine NN 1021 1023 at at IN 1024 1027 the the DT 1028 1036 carboxyl carboxyl NN 1037 1040 end end NN 1041 1043 of of IN 1044 1047 the the DT 1048 1059 cytoplasmic cytoplasmic JJ 1060 1064 tail tail NN 1065 1073 cripples cripple VBZ 1074 1077 the the DT 1078 1085 ability ability NN 1086 1088 of of IN 1089 1092 EBV EBV NNP 1093 1095 to to TO 1096 1101 cause cause VB 1102 1116 lymphoblastoid lymphoblastoid JJ 1117 1121 cell cell NN 1122 1131 outgrowth outgrowth NN 1131 1132 , , , 1133 1140 thereby thereby RB 1141 1148 marking mark VBG 1149 1150 a a DT 1151 1157 second second JJ 1158 1172 transformation transformation NN 1173 1181 effector effector NN 1182 1186 site site NN 1186 1187 , , , 1188 1192 TES2 TES2 NNP 1192 1193 . . . 1194 1195 A a DT 1196 1201 yeast yeast NN 1202 1212 two-hybrid two-hybrid JJ 1213 1219 screen screen NN 1220 1230 identified identify VBD 1231 1235 TES2 tes2 NN 1236 1247 interacting interacting NN 1248 1256 proteins protein NNS 1256 1257 , , , 1258 1267 including include VBG 1268 1271 the the DT 1272 1277 tumor tumor NN 1278 1286 necrosis necrosis NN 1287 1293 factor factor NN 1294 1313 receptor-associated receptor-associated JJ 1314 1319 death death NN 1320 1326 domain domain NN 1327 1334 protein protein NN 1335 1336 ( ( ( 1336 1341 TRADD TRADD NNP 1341 1342 ) ) ) 1342 1343 . . . 1344 1349 TRADD TRADD NNP 1350 1353 was be VBD 1354 1357 the the DT 1358 1362 only only JJ 1363 1370 protein protein NN 1371 1375 that that WDT 1376 1386 interacted interact VBD 1387 1391 with with IN 1392 1401 wild-type wild-type JJ 1402 1406 TES2 tes2 NN 1407 1410 and and CC 1411 1414 not not RB 1415 1419 with with IN 1420 1438 isoleucine-mutated isoleucine-mutated JJ 1439 1443 TES2 tes2 NN 1443 1444 . . . 1445 1450 TRADD TRADD NNP 1451 1461 associated associate VBN 1462 1466 with with IN 1467 1476 wild-type wild-type JJ 1477 1481 LMP1 lmp1 NN 1482 1485 but but CC 1486 1489 not not RB 1490 1494 with with IN 1495 1513 isoleucine-mutated isoleucine-mutated JJ 1514 1518 LMP1 lmp1 NN 1519 1521 in in IN 1522 1531 mammalian mammalian JJ 1532 1537 cells cell NNS 1537 1538 , , , 1539 1542 and and CC 1543 1548 TRADD tradd NN 1549 1563 constitutively constitutively RB 1564 1574 associated associate VBN 1575 1579 with with IN 1580 1584 LMP1 lmp1 NN 1585 1587 in in IN 1588 1603 EBV-transformed ebv-transformed JJ 1604 1609 cells cell NNS 1609 1610 . . . 1611 1613 In in IN 1614 1626 transfection transfection NN 1627 1633 assays assay NNS 1633 1634 , , , 1635 1640 TRADD TRADD NNP 1641 1644 and and CC 1645 1649 TES2 TES2 NNP 1650 1665 synergistically synergistically RB 1666 1674 mediated mediate VBD 1675 1685 high-level high-level JJ 1686 1695 NF-kappaB nf-kappab NN 1696 1706 activation activation NN 1706 1707 . . . 1708 1713 These these DT 1714 1721 results result NNS 1722 1730 indicate indicate VBP 1731 1735 that that IN 1736 1740 LMP1 lmp1 NN 1741 1753 appropriates appropriate VBZ 1754 1759 TRADD tradd NN 1760 1762 to to TO 1763 1769 enable enable VB 1770 1779 efficient efficient JJ 1780 1789 long-term long-term JJ 1790 1804 lymphoblastoid lymphoblastoid JJ 1805 1809 cell cell NN 1810 1819 outgrowth outgrowth NN 1819 1820 . . . 1821 1831 High-level high-level JJ 1832 1841 NF-kappaB NF-kappaB NNP 1842 1852 activation activation NN 1853 1857 also also RB 1858 1865 appears appear VBZ 1866 1868 to to TO 1869 1871 be be VB 1872 1873 a a DT 1874 1882 critical critical JJ 1883 1892 component component NN 1893 1895 of of IN 1896 1905 long-term long-term JJ 1906 1915 outgrowth outgrowth NN 1915 1916 . . .