0 10 Activation Activation NNP 11 13 of of IN 14 26 E2F-mediated e2f-mediated JJ 27 40 transcription transcription NN 41 43 by by IN 44 49 human human JJ 50 56 T-cell t-cell NN 57 65 leukemia leukemia NN 66 71 virus virus NN 72 76 type type NN 77 78 I i CD 79 82 Tax Tax NNP 83 90 protein protein NN 91 93 in in IN 94 95 a a DT 96 115 p16(INK4A)-negative p16(ink4a)-negative JJ 116 122 T-cell t-cell NN 123 127 line line NN 127 128 . . . 130 133 The the DT 134 139 human human JJ 140 146 T-cell t-cell NN 147 155 leukemia leukemia NN 156 161 virus virus NN 162 166 type type NN 167 168 I i CD 169 170 ( ( ( 170 176 HTLV-I HTLV-I NNP 176 177 ) ) ) 178 180 is be VBZ 181 182 a a DT 183 192 causative causative JJ 193 198 agent agent NN 199 201 of of IN 202 207 adult adult JJ 208 214 T-cell t-cell NN 215 223 leukemia leukemia NN 223 224 . . . 225 233 Although although IN 234 237 the the DT 238 243 exact exact JJ 244 253 mechanism mechanism NN 254 256 by by IN 257 262 which which WDT 263 269 HTLV-I HTLV-I NNP 270 281 contributes contribute VBZ 282 284 to to TO 285 299 leukemogenesis leukemogenesis NN 300 302 is be VBZ 303 308 still still RB 309 316 unclear unclear JJ 316 317 , , , 318 321 the the DT 322 325 Tax Tax NNP 326 333 protein protein NN 334 336 is be VBZ 337 344 thought think VBN 345 347 to to TO 348 352 play play VB 353 354 a a DT 355 360 major major JJ 361 365 role role NN 366 368 in in IN 369 373 this this DT 374 381 process process NN 381 382 . . . 383 387 This this DT 388 394 40-kDa 40-kda JJ 395 406 polypeptide polypeptide NN 407 409 is be VBZ 410 414 able able JJ 415 417 to to TO 418 426 interact interact VB 427 431 with with IN 432 435 the the DT 436 441 tumor tumor NN 442 452 suppressor suppressor NN 453 463 p16(INK4A) p16(ink4a) NN 463 464 . . . 465 477 Consequently consequently RB 477 478 , , , 479 482 Tax Tax NNP 483 486 can can MD 487 495 activate activate VB 496 499 the the DT 500 509 signaling signaling NN 510 517 pathway pathway NN 518 522 that that WDT 523 527 lead lead VBP 528 530 to to TO 531 534 the the DT 535 542 release release NN 543 545 of of IN 546 549 E2F E2F NNP 550 554 that that IN 555 557 in in IN 558 562 turn turn NN 563 570 induces induce VBZ 571 581 expression expression NN 582 584 of of IN 585 592 factors factor NNS 593 601 required require VBN 602 605 for for IN 606 610 cell cell NN 611 616 cycle cycle NN 617 628 progression progression NN 628 629 . . . 630 632 In in IN 633 637 this this DT 638 643 paper paper NN 643 644 , , , 645 647 we we PRP 648 659 demonstrate demonstrate VBP 660 664 that that IN 665 668 Tax Tax NNP 669 672 can can MD 673 677 also also RB 678 686 activate activate VB 687 699 E2F-mediated e2f-mediated JJ 700 713 transcription transcription NN 714 727 independently independently RB 728 730 of of IN 731 741 p16(INK4A) p16(ink4a) NN 741 742 . . . 743 749 Indeed indeed RB 749 750 , , , 751 755 when when WRB 756 759 Tax Tax NNP 760 762 is be VBZ 763 774 coexpressed coexpresse VBN 775 779 with with IN 780 783 the the DT 784 789 E2F-1 e2f-1 NN 790 803 transcription transcription NN 804 810 factor factor NN 811 813 in in IN 814 817 CEM CEM NNP 818 825 T-cells T-cell NNP 825 826 , , , 827 832 which which WDT 833 837 lack lack VBP 838 848 expression expression NN 849 851 of of IN 852 862 p16(INK4A) p16(INK4A) NNP 862 863 , , , 864 866 it it PRP 867 875 strongly strongly RB 876 887 potentiates potentiate VBZ 888 891 the the DT 892 905 E2F-dependent e2f-dependent JJ 906 916 activation activation NN 917 919 of of IN 920 921 a a DT 922 930 reporter reporter NN 931 940 construct construct NN 941 947 driven drive VBN 948 950 by by IN 951 952 a a DT 953 961 promoter promoter NN 962 972 containing contain VBG 973 976 E2F e2f NN 977 984 binding binding NN 985 990 sites site NNS 990 991 . . . 992 996 This this DT 997 1008 stimulation stimulation NN 1009 1011 is be VBZ 1012 1021 abrogated abrogate VBN 1022 1024 by by IN 1025 1034 mutations mutation NNS 1035 1044 affecting affect VBG 1045 1048 the the DT 1049 1060 E2F-binding e2f-binding JJ 1061 1066 sites site NNS 1066 1067 . . . 1068 1070 In in IN 1071 1079 addition addition NN 1079 1080 , , , 1081 1084 Tax Tax NNP 1085 1089 also also RB 1090 1100 stimulates stimulate VBZ 1101 1104 the the DT 1105 1118 transcription transcription NN 1119 1121 of of IN 1122 1125 the the DT 1126 1131 E2F-1 e2f-1 NN 1132 1136 gene gene NN 1137 1143 itself itself PRP 1143 1144 . . . 1145 1150 Using use VBG 1151 1154 Tax Tax NNP 1155 1162 mutants mutant NNS 1163 1167 that that WDT 1168 1172 fail fail VBP 1173 1175 to to TO 1176 1184 activate activate VB 1185 1191 either either CC 1192 1196 ATF- atf- NN 1197 1199 or or CC 1200 1219 NF-kappaB-dependent nf-kappab-dependent JJ 1220 1229 promoters promoter NNS 1230 1233 and and CC 1234 1243 different different JJ 1244 1245 5 5 CD 1245 1246 ’ ' SYM 1247 1257 truncation truncation NN 1258 1265 mutants mutant NNS 1266 1268 of of IN 1269 1272 the the DT 1273 1278 E2F-1 e2f-1 NN 1279 1287 promoter promoter NN 1287 1288 , , , 1289 1291 we we PRP 1292 1296 show show VBP 1297 1301 that that IN 1302 1305 the the DT 1306 1319 Tax-dependent tax-dependent JJ 1320 1335 transcriptional transcriptional JJ 1336 1343 control control NN 1344 1346 of of IN 1347 1350 the the DT 1351 1355 E2F1 e2f1 NN 1356 1360 gene gene NN 1361 1369 involves involve VBZ 1369 1370 , , , 1371 1373 at at IN 1374 1379 least least JJS 1380 1382 in in IN 1383 1387 part part NN 1387 1388 , , , 1389 1392 the the DT 1393 1396 ATF ATF NNP 1397 1404 binding binding NN 1405 1409 site site NN 1410 1417 located located JJ 1418 1420 in in IN 1421 1424 the the DT 1425 1430 E2F-1 e2f-1 NN 1431 1439 promoter promoter NN 1439 1440 . . .