0 10 Modulation modulation NN 11 13 of of IN 14 20 normal normal JJ 21 30 erythroid erythroid JJ 31 46 differentiation differentiation NN 47 49 by by IN 50 53 the the DT 54 64 endogenous endogenous JJ 65 72 thyroid thyroid NN 73 80 hormone hormone NN 81 84 and and CC 85 93 retinoic retinoic JJ 94 98 acid acid NN 99 108 receptors receptor NNS 108 109 : : : 110 111 a a DT 112 120 possible possible JJ 121 127 target target NN 128 131 for for IN 132 138 v-erbA v-erba NN 139 147 oncogene oncogene NN 148 154 action action NN 154 155 . . . 157 160 The the DT 161 167 v-erbA v-erba NN 168 176 oncogene oncogene NN 176 177 , , , 178 179 a a DT 180 187 mutated mutate VBN 188 195 version version NN 196 198 of of IN 199 202 the the DT 203 210 thyroid thyroid NN 211 218 hormone hormone NN 219 227 receptor receptor NN 228 233 alpha alpha NN 234 235 ( ( ( 235 250 c-erbA/TR-alpha c-erba/tr-alpha NN 250 251 ) ) ) 251 252 , , , 253 261 inhibits inhibit VBZ 262 271 erythroid erythroid JJ 272 287 differentiation differentiation NN 288 291 and and CC 292 306 constitutively constitutively RB 307 316 represses repress VBZ 317 330 transcription transcription NN 331 333 of of IN 334 341 certain certain JJ 342 353 erythrocyte erythrocyte NN 354 359 genes gene NNS 359 360 , , , 361 371 suggesting suggest VBG 372 373 a a DT 374 380 normal normal JJ 381 389 function function NN 390 392 of of IN 393 396 the the DT 397 411 proto-oncogene proto-oncogene NN 412 418 c-erbA c-erba NN 419 421 in in IN 422 436 erythropoiesis erythropoiesis NN 436 437 . . . 438 442 Here here RB 443 445 we we PRP 446 457 demonstrate demonstrate VBP 458 462 that that IN 463 466 the the DT 467 477 endogenous endogenous JJ 478 485 thyroid thyroid NN 486 493 hormone hormone NN 494 502 receptor receptor NN 503 508 alpha alpha NN 509 510 ( ( ( 510 525 c-erbA/TR-alpha c-erba/tr-alpha NN 525 526 ) ) ) 527 530 and and CC 531 534 the the DT 535 542 closely closely RB 543 550 related related JJ 551 559 retinoic retinoic JJ 560 564 acid acid NN 565 573 receptor receptor NN 574 579 alpha alpha NN 580 581 ( ( ( 581 590 RAR-alpha RAR-alpha NNP 590 591 ) ) ) 592 596 play play VBP 597 598 a a DT 599 603 role role NN 604 606 in in IN 607 610 the the DT 611 621 regulation regulation NN 622 624 of of IN 625 631 normal normal JJ 632 641 erythroid erythroid JJ 642 657 differentiation differentiation NN 657 658 . . . 659 667 Retinoic retinoic JJ 668 672 acid acid NN 673 674 ( ( ( 674 676 RA RA NNP 676 677 ) ) ) 678 688 distinctly distinctly RB 689 698 modulated modulate VBD 699 702 the the DT 703 712 erythroid erythroid JJ 713 728 differentiation differentiation NN 729 736 program program NN 737 739 of of IN 740 746 normal normal JJ 747 756 erythroid erythroid JJ 757 768 progenitors progenitor NNS 769 772 and and CC 773 786 erythroblasts erythroblast NNS 787 797 reversibly reversibly RB 798 809 transformed transform VBN 810 812 by by IN 813 814 a a DT 815 826 conditional conditional JJ 827 835 tyrosine tyrosine NN 836 842 kinase kinase NNP 843 851 oncogene oncogene NN 851 852 . . . 853 857 When when WRB 858 863 added add VBN 864 873 pulsewise pulsewise RB 874 876 to to TO 877 885 immature immature JJ 886 891 cells cell NNS 891 892 , , , 893 908 differentiation differentiation NN 909 912 was be VBD 913 924 accelerated accelerate VBN 925 930 while while IN 931 935 more more RBR 936 942 mature mature JJ 943 948 cells cell NNS 949 958 underwent undergo VBD 959 968 premature premature JJ 969 973 cell cell NN 974 979 death death NN 979 980 . . . 981 988 Thyroid thyroid NN 989 996 hormone hormone NN 997 998 ( ( ( 998 1000 T3 T3 NNP 1000 1001 ) ) ) 1002 1007 alone alone RB 1008 1014 caused cause VBD 1015 1022 similar similar JJ 1023 1026 but but CC 1027 1033 weaker weak JJR 1034 1041 effects effect NNS 1041 1042 . . . 1043 1056 Interestingly interestingly RB 1056 1057 , , , 1058 1060 T3 T3 NNP 1061 1069 strongly strongly RB 1070 1078 enhanced enhance VBD 1079 1082 the the DT 1083 1089 action action NN 1090 1092 of of IN 1093 1095 RA RA NNP 1095 1096 , , , 1097 1107 suggesting suggest VBG 1108 1119 cooperative cooperative JJ 1120 1126 action action NN 1127 1129 of of IN 1130 1133 the the DT 1134 1137 two two CD 1138 1147 receptors receptor NNS 1148 1150 in in IN 1151 1161 modulating modulate VBG 1162 1171 erythroid erythroid JJ 1172 1187 differentiation differentiation NN 1187 1188 . . . 1189 1199 Expression expression NN 1200 1202 of of IN 1203 1206 the the DT 1207 1212 human human JJ 1213 1222 RAR-alpha RAR-alpha NNP 1223 1225 in in IN 1226 1243 receptor-negative receptor-negative JJ 1244 1257 erythroblasts erythroblast NNS 1258 1267 conferred confer VBD 1268 1278 RA-induced ra-induced JJ 1279 1289 regulation regulation NN 1290 1292 of of IN 1293 1308 differentiation differentiation NN 1309 1311 to to TO 1312 1315 the the DT 1316 1325 otherwise otherwise RB 1326 1338 unresponsive unresponsive JJ 1339 1344 cells cell NNS 1344 1345 , , , 1346 1350 thus thus RB 1351 1358 showing show VBG 1359 1363 that that IN 1364 1367 the the DT 1368 1377 RAR-alpha RAR-alpha NNP 1378 1380 is be VBZ 1381 1390 essential essential JJ 1391 1394 for for IN 1395 1398 the the DT 1399 1401 RA RA NNP 1402 1408 effect effect NN 1408 1409 . . . 1410 1418 Likewise likewise RB 1418 1419 , , , 1420 1428 enhanced enhance VBN 1429 1439 expression expression NN 1440 1442 of of IN 1443 1452 exogenous exogenous JJ 1453 1468 c-erbA/TR-alpha c-erba/tr-alpha NN 1469 1471 in in IN 1472 1485 erythroblasts erythroblast NNS 1486 1494 rendered render VBD 1495 1499 them them PRP 1500 1511 susceptible susceptible JJ 1512 1514 to to TO 1515 1525 modulation modulation NN 1526 1528 of of IN 1529 1544 differentiation differentiation NN 1545 1547 by by IN 1548 1550 T3 T3 NNP 1550 1551 , , , 1552 1562 suggesting suggest VBG 1563 1564 a a DT 1565 1572 similar similar JJ 1573 1581 function function NN 1582 1584 of of IN 1585 1589 both both DT 1590 1599 receptors receptor NNS 1599 1600 . . .