0 11 Comparative comparative JJ 12 20 analysis analysis NN 21 31 identifies identify VBZ 32 41 conserved conserve VBN 42 47 tumor tumor NN 48 56 necrosis necrosis NN 57 63 factor factor NN 64 83 receptor-associated receptor-associated JJ 84 90 factor factor NN 91 92 3 3 CD 93 100 binding bind VBG 101 106 sites site NNS 107 109 in in IN 110 113 the the DT 114 119 human human JJ 120 123 and and CC 124 130 simian simian JJ 131 143 Epstein-Barr epstein-barr JJ 144 149 virus virus NN 150 158 oncogene oncogene NN 159 163 LMP1 lmp1 NN 163 164 . . . 166 174 Nonhuman nonhuman JJ 175 183 primates primate NNS 184 187 are be VBP 188 197 naturally naturally RB 198 206 infected infect VBN 207 211 with with IN 212 213 a a DT 214 228 B-lymphotropic b-lymphotropic JJ 229 240 herpesvirus herpesvirus NN 241 248 closely closely RB 249 256 related related JJ 257 259 to to TO 260 272 Epstein-Barr epstein-barr JJ 273 278 virus virus NN 279 280 ( ( ( 280 283 EBV EBV NNP 283 284 ) ) ) 284 285 . . . 286 291 These these DT 292 298 simian simian JJ 299 302 EBV EBV NNP 303 308 share share NN 309 321 considerable considerable JJ 322 329 genetic genetic JJ 329 330 , , , 331 339 biologic biologic JJ 339 340 , , , 341 344 and and CC 345 358 epidemiologic epidemiologic JJ 359 367 features feature NNS 368 372 with with IN 373 378 human human JJ 379 382 EBV EBV NNP 382 383 , , , 384 393 including include VBG 394 407 virus-induced virus-induced JJ 408 421 tumorigenesis tumorigenesis NN 421 422 . . . 423 430 However however RB 430 431 , , , 432 438 latent latent JJ 438 439 , , , 440 465 transformation-associated transformation-associated JJ 466 471 viral viral JJ 472 477 genes gene NNS 478 489 demonstrate demonstrate VBP 490 496 marked marked JJ 497 505 sequence sequence NN 506 516 divergence divergence NN 517 522 among among IN 523 530 species specie NNS 531 538 despite despite IN 539 542 the the DT 543 552 conserved conserve VBN 553 562 functions function NNS 562 563 . . . 564 566 We we PRP 567 571 have have VBP 572 578 cloned clone VBN 579 582 the the DT 583 589 latent latent JJ 590 598 membrane membrane NN 599 606 protein protein NN 607 608 1 1 CD 609 610 ( ( ( 610 614 LMP1 lmp1 NN 614 615 ) ) ) 616 624 homologs homolog NNS 625 629 from from IN 630 633 the the DT 634 640 simian simian JJ 641 644 EBV ebv NN 645 654 naturally naturally RB 655 664 infecting infect VBG 665 672 baboons baboon NNS 673 674 ( ( ( 674 688 cercopithicine cercopithicine NN 689 700 herpesvirus herpesvirus NN 701 703 12 12 CD 703 704 , , , 705 716 herpesvirus herpesvirus NN 717 722 papio papio NN 722 723 ) ) ) 724 727 and and CC 728 734 rhesus rhesus NN 735 742 monkeys monkey NNS 743 744 ( ( ( 744 758 cercopithicine cercopithicine NN 759 770 herpesvirus herpesvirus NN 771 773 15 15 CD 773 774 ) ) ) 775 778 for for IN 779 780 a a DT 781 792 comparative comparative JJ 793 798 study study NN 799 803 with with IN 804 807 the the DT 808 813 human human JJ 814 817 EBV EBV NNP 818 826 oncogene oncogene NN 826 827 . . . 828 831 The the DT 832 845 transmembrane transmembrane NN 846 853 domains domain NNS 854 857 are be VBP 858 862 well well RB 863 872 conserved conserve VBN 872 873 , , , 874 877 but but CC 878 883 there there EX 884 886 is be VBZ 887 895 striking striking JJ 896 904 sequence sequence NN 905 915 divergence divergence NN 916 918 of of IN 919 922 the the DT 923 939 carboxy-terminal carboxy-terminal JJ 940 951 cytoplasmic cytoplasmic JJ 952 958 domain domain NN 959 968 essential essential JJ 969 972 for for IN 973 979 B-cell b-cell NN 980 995 immortalization immortalization NN 996 999 and and CC 1000 1011 interaction interaction NN 1012 1016 with with IN 1017 1020 the the DT 1021 1026 tumor tumor NN 1027 1035 necrosis necrosis NN 1036 1042 factor factor NN 1043 1051 receptor receptor NN 1052 1061 signaling signaling NN 1062 1069 pathway pathway NN 1069 1070 . . . 1071 1083 Nevertheless nevertheless RB 1083 1084 , , , 1085 1088 the the DT 1089 1095 simian simian JJ 1096 1099 EBV EBV NNP 1100 1105 LMP1s LMP1 NNP 1106 1112 retain retain VBP 1113 1117 most most JJS 1118 1127 functions function NNS 1128 1130 in in IN 1131 1137 common common JJ 1138 1142 with with IN 1143 1146 EBV EBV NNP 1147 1151 LMP1 LMP1 NNP 1151 1152 , , , 1153 1162 including include VBG 1163 1166 the the DT 1167 1174 ability ability NN 1175 1177 to to TO 1178 1184 induce induce VB 1185 1196 NF-(kappa)B NF-(kappa)B NNP 1197 1205 activity activity NN 1206 1208 in in IN 1209 1214 human human JJ 1215 1220 cells cell NNS 1220 1221 , , , 1222 1224 to to TO 1225 1229 bind bind VB 1230 1233 the the DT 1234 1239 tumor tumor NN 1240 1248 necrosis necrosis NN 1249 1266 factor-associated factor-associated JJ 1267 1273 factor factor NN 1274 1275 3 3 CD 1276 1277 ( ( ( 1277 1282 TRAF3 traf3 NN 1282 1283 ) ) ) 1284 1286 in in FW 1287 1292 vitro vitro FW 1292 1293 , , , 1294 1297 and and CC 1298 1300 to to TO 1301 1307 induce induce VB 1308 1318 expression expression NN 1319 1321 of of IN 1322 1327 tumor tumor NN 1328 1336 necrosis necrosis NN 1337 1354 factor-responsive factor-responsive JJ 1355 1360 genes gene NNS 1360 1361 , , , 1362 1366 such such JJ 1367 1369 as as IN 1370 1375 ICAM1 ICAM1 NNP 1375 1376 , , , 1377 1379 in in IN 1380 1385 human human JJ 1386 1387 B B NNP 1388 1399 lymphocytes lymphocyte NNS 1399 1400 . . . 1401 1409 Multiple multiple JJ 1410 1415 TRAF3 traf3 NN 1416 1423 binding binding NN 1424 1429 sites site NNS 1430 1440 containing contain VBG 1441 1442 a a DT 1443 1450 PXQXT/S PXQXT/S NNP 1451 1455 core core NN 1456 1464 sequence sequence NN 1465 1468 can can MD 1469 1471 be be VB 1472 1482 identified identify VBN 1483 1485 in in IN 1486 1489 the the DT 1490 1496 simian simian JJ 1497 1500 EBV EBV NNP 1501 1506 LMP1s LMP1 NNP 1507 1509 by by IN 1510 1512 an an DT 1513 1515 in in FW 1516 1521 vitro vitro FW 1522 1529 binding binding NN 1530 1535 assay assay NN 1535 1536 . . . 1537 1538 A a DT 1539 1557 PXQXT/S-containing pxqxt/s-containing JJ 1558 1566 sequence sequence NN 1567 1569 is be VBZ 1570 1574 also also RB 1575 1582 present present JJ 1583 1585 in in IN 1586 1589 the the DT 1590 1601 cytoplasmic cytoplasmic JJ 1602 1608 domain domain NN 1609 1611 of of IN 1612 1615 the the DT 1616 1623 Hodgkin Hodgkin NNP 1623 1625 ’s 's POS 1626 1633 disease disease NN 1634 1640 marker marker NN 1640 1641 , , , 1642 1646 CD30 CD30 NNP 1646 1647 , , , 1648 1651 and and CC 1652 1657 binds bind VBZ 1658 1663 TRAF3 traf3 NN 1664 1666 in in FW 1667 1672 vitro vitro FW 1672 1673 . . . 1674 1677 The the DT 1678 1682 last last JJ 1683 1685 13 13 CD 1686 1691 amino amino NN 1692 1697 acids acid NNS 1698 1708 containing contain VBG 1709 1710 a a DT 1711 1718 PXQXT/S PXQXT/S NNP 1719 1727 sequence sequence NN 1728 1731 are be VBP 1732 1738 highly highly RB 1739 1748 conserved conserve VBN 1749 1751 in in IN 1752 1757 human human JJ 1758 1761 and and CC 1762 1768 simian simian JJ 1769 1772 EBV EBV NNP 1773 1777 LMP1 LMP1 NNP 1778 1781 but but CC 1782 1784 do do VBP 1785 1788 not not RB 1789 1793 bind bind VB 1794 1799 TRAF3 traf3 NN 1799 1800 , , , 1801 1811 suggesting suggest VBG 1812 1813 a a DT 1814 1822 distinct distinct JJ 1823 1827 role role NN 1828 1831 for for IN 1832 1836 this this DT 1837 1846 conserved conserve VBN 1847 1853 region region NN 1854 1856 of of IN 1857 1861 LMP1 LMP1 NNP 1861 1862 . . . 1863 1866 The the DT 1867 1876 conserved conserve VBN 1877 1882 TRAF3 traf3 NN 1883 1890 binding binding NN 1891 1896 sites site NNS 1897 1899 in in IN 1900 1904 LMP1 LMP1 NNP 1905 1908 and and CC 1909 1912 the the DT 1913 1917 CD30 CD30 NNP 1918 1925 Hodgkin Hodgkin NNP 1925 1927 ’s 's POS 1928 1935 disease disease NN 1936 1942 marker marker NN 1943 1951 provides provide VBZ 1952 1959 further further JJ 1960 1968 evidence evidence NN 1969 1973 that that IN 1974 1975 a a DT 1976 1990 TRAF3-mediated traf3-mediated JJ 1991 1997 signal signal NN 1998 2010 transduction transduction NN 2011 2018 pathway pathway NN 2019 2022 may may MD 2023 2025 be be VB 2026 2035 important important JJ 2036 2038 in in IN 2039 2048 malignant malignant JJ 2049 2063 transformation transformation NN 2063 2064 . . .