0 12 Inactivation inactivation NN 13 15 of of IN 16 27 IkappaBbeta IkappaBbeta NNP 28 30 by by IN 31 34 the the DT 35 38 tax tax NN 39 46 protein protein NN 47 49 of of IN 50 55 human human JJ 56 62 T-cell t-cell NN 63 71 leukemia leukemia NN 72 77 virus virus NN 78 82 type type NN 83 84 1 1 CD 84 85 : : : 86 87 a a DT 88 97 potential potential JJ 98 107 mechanism mechanism NN 108 111 for for IN 112 124 constitutive constitutive JJ 125 134 induction induction NN 135 137 of of IN 138 147 NF-kappaB NF-kappaB NNP 147 148 . . . 150 152 In in IN 153 160 resting rest VBG 161 162 T t NN 163 174 lymphocytes lymphocyte NNS 174 175 , , , 176 179 the the DT 180 193 transcription transcription NN 194 200 factor factor NN 201 210 NF-kappaB NF-kappaB NNP 211 213 is be VBZ 214 225 sequestered sequester VBN 226 228 in in IN 229 232 the the DT 233 242 cytoplasm cytoplasm NN 243 246 via via IN 247 259 interactions interaction NNS 260 264 with with IN 265 272 members member NNS 273 275 of of IN 276 279 the the DT 280 281 I i NN 282 287 kappa kappa NN 288 289 B B NNP 290 296 family family NN 297 299 of of IN 300 310 inhibitors inhibitor NNS 310 311 , , , 312 321 including include VBG 322 334 IkappaBalpha IkappaBalpha NNP 335 338 and and CC 339 350 IkappaBbeta IkappaBbeta NNP 350 351 . . . 352 358 During during IN 359 365 normal normal JJ 366 372 T-cell t-cell NN 373 383 activation activation NN 383 384 , , , 385 397 IkappaBalpha IkappaBalpha NNP 398 400 is be VBZ 401 408 rapidly rapidly RB 409 423 phosphorylated phosphorylate VBN 423 424 , , , 425 438 ubiquitinated ubiquitinate VBN 438 439 , , , 440 443 and and CC 444 452 degraded degrade VBN 453 455 by by IN 456 459 the the DT 460 463 26S 26s NN 464 474 proteasome proteasome NN 474 475 , , , 476 480 thus thus RB 481 491 permitting permit VBG 492 495 the the DT 496 503 release release NN 504 506 of of IN 507 517 functional functional JJ 518 527 NF-kappaB nf-kappab NN 527 528 . . . 529 531 In in IN 532 540 contrast contrast NN 541 543 to to TO 544 547 its its PRP$ 548 557 transient transient JJ 558 565 pattern pattern NN 566 568 of of IN 569 576 nuclear nuclear JJ 577 586 induction induction NN 587 593 during during IN 594 596 an an DT 597 603 immune immune JJ 604 612 response response NN 612 613 , , , 614 623 NF-kappaB NF-kappaB NNP 624 626 is be VBZ 627 641 constitutively constitutively RB 642 651 activated activate VBN 652 654 in in IN 655 660 cells cell NNS 661 671 expressing express VBG 672 675 the the DT 676 679 Tax tax NN 680 692 transforming transforming NN 693 700 protein protein NN 701 703 of of IN 704 709 human human JJ 710 716 T-cell t-cell NN 717 725 leukemia leukemia NN 726 731 virus virus NN 732 736 type type NN 737 738 I i CD 739 740 ( ( ( 740 746 HTLV-1 HTLV-1 NNP 746 747 ) ) ) 747 748 . . . 749 755 Recent recent JJ 756 763 studies study NNS 764 772 indicate indicate VBP 773 777 that that IN 778 784 HTLV-1 HTLV-1 NNP 785 788 Tax Tax NNP 789 796 targets target VBZ 797 809 IkappaBalpha IkappaBalpha NNP 810 812 to to TO 813 816 the the DT 817 837 ubiquitin-proteasome ubiquitin-proteasome JJ 838 845 pathway pathway NN 845 846 . . . 847 854 However however RB 854 855 , , , 856 858 it it PRP 859 866 remains remain VBZ 867 874 unclear unclear JJ 875 878 how how WRB 879 883 this this DT 884 889 viral viral JJ 890 897 protein protein NN 898 905 induces induce VBZ 906 907 a a DT 908 918 persistent persistent JJ 919 925 rather rather RB 926 930 than than IN 931 940 transient transient JJ 941 950 NF-kappaB NF-kappaB NNP 951 959 response response NN 959 960 . . . 961 963 In in IN 964 968 this this DT 969 975 report report NN 975 976 , , , 977 979 we we PRP 980 987 provide provide VBP 988 996 evidence evidence NN 997 1001 that that IN 1002 1004 in in IN 1005 1013 addition addition NN 1014 1016 to to TO 1017 1023 acting act VBG 1024 1026 on on IN 1027 1039 IkappaBalpha IkappaBalpha NNP 1039 1040 , , , 1041 1044 Tax Tax NNP 1045 1055 stimulates stimulate VBZ 1056 1059 the the DT 1060 1068 turnover turnover NN 1069 1071 Of of IN 1072 1083 IkappaBbeta IkappaBbeta NNP 1084 1087 via via IN 1088 1089 a a DT 1090 1097 related related JJ 1098 1107 targeting targeting NN 1108 1117 mechanism mechanism NN 1117 1118 . . . 1119 1123 Like like IN 1124 1136 IkappaBalpha IkappaBalpha NNP 1136 1137 , , , 1138 1150 Tax-mediated tax-mediated JJ 1151 1160 breakdown breakdown NN 1161 1163 of of IN 1164 1175 IkappaBbeta IkappaBbeta NNP 1176 1178 in in IN 1179 1190 transfected transfecte VBN 1191 1192 T t NN 1193 1204 lymphocytes lymphocyte NNS 1205 1207 is be VBZ 1208 1215 blocked block VBN 1216 1222 either either CC 1223 1225 by by IN 1226 1240 cell-permeable cell-permeable JJ 1241 1251 proteasome proteasome NN 1252 1262 inhibitors inhibitor NNS 1263 1265 or or CC 1266 1268 by by IN 1269 1277 mutation mutation NN 1278 1280 Of of IN 1281 1292 IkappaBbeta IkappaBbeta NNP 1293 1295 at at IN 1296 1299 two two CD 1300 1306 serine serine NN 1307 1315 residues residue NNS 1316 1323 present present JJ 1324 1330 within within IN 1331 1334 its its PRP$ 1335 1345 N-terminal n-terminal JJ 1346 1352 region region NN 1352 1353 . . . 1354 1361 Despite despite IN 1362 1365 the the DT 1366 1370 dual dual JJ 1371 1382 specificity specificity NN 1383 1385 of of IN 1386 1392 HTLV-1 HTLV-1 NNP 1393 1396 Tax Tax NNP 1397 1400 for for IN 1401 1413 IkappaBalpha IkappaBalpha NNP 1414 1417 and and CC 1418 1429 IkappaBbeta IkappaBbeta NNP 1430 1432 at at IN 1433 1436 the the DT 1437 1444 protein protein NN 1445 1450 level level NN 1450 1451 , , , 1452 1455 Tax Tax NNP 1456 1467 selectively selectively RB 1468 1478 stimulates stimulate VBZ 1479 1497 NF-kappaB-directed nf-kappab-directed JJ 1498 1511 transcription transcription NN 1512 1514 of of IN 1515 1518 the the DT 1519 1531 IkappaBalpha IkappaBalpha NNP 1532 1536 gene gene NN 1536 1537 . . . 1538 1550 Consequently consequently RB 1550 1551 , , , 1552 1563 IkappaBbeta IkappaBbeta NNP 1564 1571 protein protein NN 1572 1582 expression expression NN 1583 1585 is be VBZ 1586 1597 chronically chronically RB 1598 1611 downregulated downregulate VBN 1612 1614 in in IN 1615 1630 HTLV-1-infected htlv-1-infected JJ 1631 1632 T t NN 1633 1644 lymphocytes lymphocyte NNS 1644 1645 . . . 1646 1651 These these DT 1652 1660 findings finding NNS 1661 1665 with with IN 1666 1677 IkappaBbeta IkappaBbeta NNP 1678 1685 provide provide VBP 1686 1687 a a DT 1688 1697 potential potential JJ 1698 1707 mechanism mechanism NN 1708 1711 for for IN 1712 1715 the the DT 1716 1728 constitutive constitutive JJ 1729 1739 activation activation NN 1740 1742 of of IN 1743 1752 NF-kappaB NF-kappaB NNP 1753 1755 in in IN 1756 1770 Tax-expressing tax-expressing JJ 1771 1776 cells cell NNS 1776 1777 . . .