0 6 Latent latent JJ 7 15 membrane membrane NN 16 25 protein-1 protein-1 NN 26 33 induces induce VBZ 34 40 cyclin cyclin NN 41 43 D2 d2 NN 44 54 expression expression NN 54 55 , , , 56 59 pRb prb NN 60 80 hyperphosphorylation hyperphosphorylation NN 80 81 , , , 82 85 and and CC 86 90 loss loss NN 91 93 of of IN 94 102 TGF-beta TGF-beta NNP 103 113 1-mediated 1-mediated JJ 114 120 growth growth NN 121 131 inhibition inhibition NN 132 134 in in IN 135 147 EBV-positive ebv-positive JJ 148 149 B B NNP 150 155 cells cell NNS 155 156 . . . 158 161 The the DT 162 168 normal normal JJ 169 173 cell cell NN 174 179 cycle cycle NN 180 182 is be VBZ 183 192 regulated regulate VBN 193 195 by by IN 196 203 several several JJ 204 213 molecules molecule NNS 213 214 , , , 215 219 such such JJ 220 222 as as IN 223 226 the the DT 227 243 tumor-suppressor tumor-suppressor JJ 244 251 protein protein NN 252 255 pRb prb NN 255 256 , , , 257 260 the the DT 261 263 G1 g1 NN 264 271 cyclins cyclin NNS 271 272 , , , 273 276 the the DT 277 293 cyclin-dependent cyclin-dependent JJ 294 301 kinases kinase NNS 301 302 , , , 303 306 and and CC 307 312 their their PRP$ 313 323 inhibitors inhibitor NNS 323 324 . . . 325 330 These these DT 331 341 regulators regulator NNS 342 345 are be VBP 346 354 targeted target VBN 355 357 by by IN 358 366 negative negative JJ 367 373 growth growth NN 374 384 regulatory regulatory JJ 385 392 signals signal NNS 392 393 , , , 394 398 such such JJ 399 401 as as IN 402 406 that that DT 407 415 provided provide VBN 416 418 by by IN 419 427 TGF-beta TGF-beta NNP 427 428 . . . 429 433 Here here RB 433 434 , , , 435 437 we we PRP 438 442 show show VBP 443 447 that that IN 448 451 the the DT 452 460 presence presence NN 461 463 of of IN 464 470 either either CC 471 480 wild-type wild-type JJ 481 484 EBV EBV NNP 485 487 or or CC 488 491 its its PRP$ 492 504 transforming transform VBG 505 511 latent latent JJ 512 520 membrane membrane NN 521 530 protein-1 protein-1 NN 531 532 ( ( ( 532 537 LMP-1 lmp-1 NN 537 538 ) ) ) 539 546 results result VBZ 547 549 in in IN 550 553 the the DT 554 558 loss loss NN 559 561 of of IN 562 570 TGF-beta TGF-beta NNP 571 581 1-mediated 1-mediated JJ 582 588 growth growth NN 589 599 inhibition inhibition NN 600 602 in in IN 603 608 human human JJ 609 610 B B NNP 611 616 cells cell NNS 616 617 . . . 618 626 Chemical chemical JJ 627 640 cross-linking cross-linking NN 641 645 with with IN 646 658 125I-labeled 125i-labeled JJ 659 667 TGF-beta TGF-beta NNP 668 669 1 1 CD 670 676 showed show VBD 677 679 an an DT 680 691 essentially essentially RB 692 698 normal normal JJ 699 707 TGF-beta TGF-beta NNP 708 716 receptor receptor NN 717 724 profile profile NN 725 727 in in IN 728 740 EBV-positive ebv-positive JJ 741 744 and and CC 745 757 EBV-negative ebv-negative JJ 758 765 Burkitt Burkitt NNP 765 767 ’s 's POS 768 776 lymphoma lymphoma NN 777 781 cell cell NN 782 787 lines line NNS 787 788 , , , 789 792 and and CC 793 798 these these DT 799 808 receptors receptor NNS 809 813 were be VBD 814 819 shown show VBN 820 822 to to TO 823 825 be be VB 826 836 functional functional JJ 837 839 in in IN 840 851 transducing transduce VBG 852 859 signals signal NNS 859 860 , , , 861 863 as as IN 864 873 evidenced evidence VBN 874 876 by by IN 877 880 the the DT 881 889 TGF-beta TGF-beta NNP 890 900 1-mediated 1-mediated JJ 901 911 modulation modulation NN 912 914 of of IN 915 919 junB junb NN 920 924 gene gene NN 925 935 expression expression NN 935 936 . . . 937 944 However however RB 944 945 , , , 946 954 TGF-beta TGF-beta NNP 955 956 1 1 CD 957 960 did do VBD 961 964 not not RB 965 971 induce induce VB 972 989 dephosphorylation dephosphorylation NN 990 992 of of IN 993 996 pRb prb NN 997 999 in in IN 1000 1003 EBV EBV NNP 1004 1005 ( ( ( 1005 1007 or or CC 1008 1023 LMP-1)-positive lmp-1)-positive JJ 1024 1029 cells cell NNS 1030 1032 as as IN 1033 1040 opposed oppose VBN 1041 1043 to to TO 1044 1056 EBV-negative ebv-negative JJ 1057 1062 cells cell NNS 1062 1063 , , , 1064 1074 suggesting suggest VBG 1075 1076 a a DT 1077 1086 dichotomy dichotomy NN 1087 1089 in in IN 1090 1093 the the DT 1094 1102 TGF-beta TGF-beta NNP 1103 1104 1 1 CD 1105 1114 signaling signaling NN 1115 1122 pathway pathway NN 1123 1130 leading lead VBG 1131 1133 to to TO 1134 1143 separable separable JJ 1144 1148 gene gene NN 1149 1159 regulatory regulatory JJ 1160 1163 and and CC 1164 1170 growth growth NN 1171 1181 inhibitory inhibitory JJ 1182 1191 responses response NNS 1191 1192 . . . 1193 1204 Furthermore furthermore RB 1204 1205 , , , 1206 1211 LMP-1 lmp-1 NN 1212 1215 was be VBD 1216 1221 found find VBN 1222 1224 to to TO 1225 1231 induce induce VB 1232 1235 the the DT 1236 1246 expression expression NN 1247 1249 of of IN 1250 1256 cyclin cyclin NN 1257 1259 D2 d2 NN 1259 1260 ; ; : 1261 1267 normal normal JJ 1268 1269 B B NNP 1270 1275 cells cell NNS 1276 1278 or or CC 1279 1291 EBV-negative ebv-negative JJ 1292 1299 Burkitt Burkitt NNP 1299 1301 ’s 's POS 1302 1310 lymphoma lymphoma NN 1311 1316 cells cell NNS 1317 1319 do do VBP 1320 1323 not not RB 1324 1331 express express VB 1332 1338 D-type d-type JJ 1339 1346 cyclins cyclin NNS 1346 1347 . . . 1348 1353 Taken take VBN 1354 1362 together together RB 1362 1363 , , , 1364 1369 these these DT 1370 1374 data datum NNS 1375 1380 point point VBP 1381 1383 to to TO 1384 1385 a a DT 1386 1395 potential potential JJ 1396 1405 mechanism mechanism NN 1406 1416 underlying underlie VBG 1417 1429 EBV-mediated ebv-mediated JJ 1430 1431 B B NNP 1432 1436 cell cell NN 1437 1451 transformation transformation NN 1452 1459 whereby whereby WRB 1460 1472 constitutive constitutive JJ 1473 1482 induction induction NN 1483 1485 of of IN 1486 1489 key key JJ 1490 1494 cell cell NN 1495 1500 cycle cycle NN 1501 1511 regulators regulator NNS 1512 1514 by by IN 1515 1520 LMP-1 lmp-1 NN 1521 1524 can can MD 1525 1529 lead lead VB 1530 1532 to to TO 1533 1536 pRb prb NN 1537 1557 hyperphosphorylation hyperphosphorylation NN 1558 1561 and and CC 1562 1574 uncontrolled uncontrolled JJ 1575 1579 cell cell NN 1580 1593 proliferation proliferation NN 1593 1594 . . .