0 14 Bcl-2-mediated bcl-2-mediated JJ 15 19 drug drug NN 20 30 resistance resistance NN 30 31 : : : 32 42 inhibition inhibition NN 43 45 of of IN 46 55 apoptosis apoptosis NN 56 58 by by IN 59 67 blocking block VBG 68 75 nuclear nuclear JJ 76 82 factor factor NN 83 85 of of IN 86 95 activated activate VBN 96 97 T t NN 98 109 lymphocytes lymphocyte NNS 110 111 ( ( ( 111 124 NFAT)-induced nfat)-induced JJ 125 128 Fas Fas NNP 129 135 ligand ligand NN 136 149 transcription transcription NN 149 150 . . . 152 157 Bcl-2 bcl-2 NN 158 166 inhibits inhibit VBZ 167 176 apoptosis apoptosis NN 177 184 induced induce VBN 185 187 by by IN 188 189 a a DT 190 197 variety variety NN 198 200 of of IN 201 208 stimuli stimulus NNS 208 209 , , , 210 219 including include VBG 220 232 chemotherapy chemotherapy NN 233 238 drugs drug NNS 239 242 and and CC 243 258 glucocorticoids glucocorticoid NNS 258 259 . . . 260 262 It it PRP 263 265 is be VBZ 266 275 generally generally RB 276 284 accepted accept VBN 285 289 that that IN 290 295 Bcl-2 bcl-2 NN 296 302 exerts exert VBZ 303 306 its its PRP$ 307 320 antiapoptotic antiapoptotic JJ 321 328 effects effect NNS 329 335 mainly mainly RB 336 338 by by IN 339 349 dimerizing dimerize VBG 350 354 with with IN 355 367 proapoptotic proapoptotic JJ 368 375 members member NNS 376 378 of of IN 379 382 the the DT 383 388 Bcl-2 bcl-2 NN 389 395 family family NN 396 400 such such JJ 401 403 as as IN 404 407 Bax Bax NNP 408 411 and and CC 412 415 Bad Bad NNP 415 416 . . . 417 424 However however RB 424 425 , , , 426 429 the the DT 430 439 mechanism mechanism NN 440 442 of of IN 443 446 the the DT 447 460 antiapoptotic antiapoptotic JJ 461 468 effects effect NNS 469 471 is be VBZ 472 479 unclear unclear JJ 479 480 . . . 481 491 Paclitaxel Paclitaxel NNP 492 495 and and CC 496 501 other other JJ 502 507 drugs drug NNS 508 512 that that WDT 513 520 disturb disturb VBP 521 532 microtubule microtubule NN 533 541 dynamics dynamic NNS 542 546 kill kill VBP 547 552 cells cell NNS 553 555 in in IN 556 557 a a DT 558 565 Fas/Fas Fas/Fas NNP 566 572 ligand ligand NN 573 574 ( ( ( 574 589 FasL)-dependent fasl)-dependent JJ 590 596 manner manner NN 596 597 ; ; : 598 606 antibody antibody NN 607 609 to to TO 610 614 FasL FasL NNP 615 623 inhibits inhibit VBZ 624 642 paclitaxel-induced paclitaxel-induced JJ 643 652 apoptosis apoptosis NN 652 653 . . . 654 656 We we PRP 657 661 have have VBP 662 667 found find VBN 668 672 that that IN 673 678 Bcl-2 bcl-2 NN 679 693 overexpression overexpression NN 694 699 leads lead VBZ 700 702 to to TO 703 706 the the DT 707 717 prevention prevention NN 718 720 of of IN 721 733 chemotherapy chemotherapy NN 734 735 ( ( ( 735 754 paclitaxel)-induced paclitaxel)-induced JJ 755 765 expression expression NN 766 768 of of IN 769 773 FasL FasL NNP 774 777 and and CC 778 784 blocks block VBZ 785 803 paclitaxel-induced paclitaxel-induced JJ 804 813 apoptosis apoptosis NN 813 814 . . . 815 818 The the DT 819 828 mechanism mechanism NN 829 831 of of IN 832 836 this this DT 837 843 effect effect NN 844 846 is be VBZ 847 851 that that IN 852 857 Bcl-2 bcl-2 NN 858 866 prevents prevent VBZ 867 870 the the DT 871 878 nuclear nuclear JJ 879 892 translocation translocation NN 893 895 of of IN 896 900 NFAT NFAT NNP 901 902 ( ( ( 902 909 nuclear nuclear JJ 910 916 factor factor NN 917 919 of of IN 920 929 activated activate VBN 930 931 T t NN 932 943 lymphocytes lymphocyte NNS 943 944 , , , 945 946 a a DT 947 960 transcription transcription NN 961 967 factor factor NN 968 977 activated activate VBN 978 980 by by IN 981 992 microtubule microtubule NN 993 999 damage damage NN 999 1000 ) ) ) 1001 1003 by by IN 1004 1011 binding bind VBG 1012 1015 and and CC 1016 1028 sequestering sequester VBG 1029 1040 calcineurin calcineurin NN 1040 1041 , , , 1042 1043 a a DT 1044 1061 calcium-dependent calcium-dependent JJ 1062 1073 phosphatase phosphatase NN 1074 1078 that that WDT 1079 1083 must must MD 1084 1099 dephosphorylate dephosphorylate VB 1100 1104 NFAT NFAT NNP 1105 1107 to to TO 1108 1112 move move VB 1113 1115 to to TO 1116 1119 the the DT 1120 1127 nucleus nucleus NN 1127 1128 . . . 1129 1136 Without without IN 1137 1141 NFAT NFAT NNP 1142 1149 nuclear nuclear JJ 1150 1163 translocation translocation NN 1163 1164 , , , 1165 1168 the the DT 1169 1173 FasL FasL NNP 1174 1178 gene gene NN 1179 1181 is be VBZ 1182 1185 not not RB 1186 1197 transcribed transcribe VBN 1197 1198 . . . 1199 1203 Thus thus RB 1203 1204 , , , 1205 1207 it it PRP 1208 1215 appears appear VBZ 1216 1220 that that IN 1221 1231 paclitaxel paclitaxel NN 1232 1235 and and CC 1236 1241 other other JJ 1242 1247 drugs drug NNS 1248 1252 that that WDT 1253 1260 disturb disturb VBP 1261 1272 microtubule microtubule NN 1273 1281 function function NN 1282 1286 kill kill NN 1287 1292 cells cell NNS 1293 1295 at at IN 1296 1301 least least JJS 1302 1304 in in IN 1305 1309 part part NN 1310 1317 through through IN 1318 1321 the the DT 1322 1331 induction induction NN 1332 1334 of of IN 1335 1339 FasL FasL NNP 1339 1340 . . . 1341 1352 Furthermore furthermore RB 1352 1353 , , , 1354 1359 Bcl-2 bcl-2 NN 1360 1371 antagonizes antagonize VBZ 1372 1384 drug-induced drug-induced JJ 1385 1394 apoptosis apoptosis NN 1395 1397 by by IN 1398 1408 inhibiting inhibit VBG 1409 1420 calcineurin calcineurin NN 1421 1431 activation activation NN 1431 1432 , , , 1433 1441 blocking block VBG 1442 1446 NFAT NFAT NNP 1447 1454 nuclear nuclear JJ 1455 1468 translocation translocation NN 1468 1469 , , , 1470 1473 and and CC 1474 1484 preventing prevent VBG 1485 1489 FasL fasl NN 1490 1500 expression expression NN 1500 1501 . . . 1502 1505 The the DT 1506 1513 effects effect NNS 1514 1516 of of IN 1517 1522 Bcl-2 bcl-2 NN 1523 1526 can can MD 1527 1529 be be VB 1530 1538 overcome overcome VBN 1538 1539 , , , 1540 1542 at at IN 1543 1548 least least JJS 1549 1558 partially partially RB 1558 1559 , , , 1560 1567 through through IN 1568 1583 phosphorylation phosphorylation NN 1584 1586 of of IN 1587 1592 Bcl-2 bcl-2 NN 1592 1593 . . . 1594 1608 Phosphorylated phosphorylate VBN 1609 1614 Bcl-2 bcl-2 NN 1615 1621 cannot cannot MD 1622 1626 bind bind VB 1627 1638 calcineurin calcineurin NN 1638 1639 , , , 1640 1643 and and CC 1644 1648 NFAT NFAT NNP 1649 1659 activation activation NN 1659 1660 , , , 1661 1665 FasL FasL NNP 1666 1676 expression expression NN 1676 1677 , , , 1678 1681 and and CC 1682 1691 apoptosis apoptosis NN 1692 1695 can can MD 1696 1701 occur occur VB 1702 1707 after after IN 1708 1713 Bcl-2 bcl-2 NN 1714 1729 phosphorylation phosphorylation NN 1729 1730 . . .