0 15 Transcriptional transcriptional JJ 16 19 and and CC 20 40 post-transcriptional post-transcriptional JJ 41 51 regulation regulation NN 52 54 of of IN 55 60 c-jun c-jun NN 61 71 expression expression NN 72 78 during during IN 79 88 monocytic monocytic JJ 89 104 differentiation differentiation NN 105 107 of of IN 108 113 human human JJ 114 121 myeloid myeloid JJ 122 130 leukemic leukemic JJ 131 136 cells cell NNS 136 137 . . . 139 143 AP-1 ap-1 NN 143 144 , , , 145 148 the the DT 149 160 polypeptide polypeptide NN 161 168 product product NN 169 171 of of IN 172 177 c-jun c-jun NN 177 178 , , , 179 189 recognizes recognize VBZ 190 193 and and CC 194 199 binds bind VBZ 200 202 to to TO 203 211 specific specific JJ 212 215 DNA dna NN 216 225 sequences sequence NNS 226 229 and and CC 230 240 stimulates stimulate VBZ 241 254 transcription transcription NN 255 257 of of IN 258 263 genes gene NNS 264 274 responsive responsive JJ 275 277 to to TO 278 285 certain certain JJ 286 292 growth growth NN 293 300 factors factor NNS 301 304 and and CC 305 312 phorbol phorbol NN 313 319 esters ester NNS 320 324 such such JJ 325 327 as as IN 328 364 12-O-tetradecanoylphorbol-13-acetate 12-O-tetradecanoylphorbol-13-acetate NNP 365 366 ( ( ( 366 369 TPA TPA NNP 369 370 ) ) ) 370 371 . . . 372 374 We we PRP 375 382 studied study VBD 383 386 the the DT 387 394 effects effect NNS 395 397 of of IN 398 401 TPA TPA NNP 402 404 on on IN 405 408 the the DT 409 419 regulation regulation NN 420 422 of of IN 423 428 c-jun c-jun NN 429 433 gene gene NN 434 444 expression expression NN 445 447 in in IN 448 453 HL-60 hl-60 NN 454 459 cells cell NNS 460 466 during during IN 467 476 monocytic monocytic JJ 477 492 differentiation differentiation NN 492 493 . . . 494 497 Low low JJ 498 504 levels level NNS 505 507 of of IN 508 513 c-jun c-jun NN 514 525 transcripts transcript NNS 526 530 were be VBD 531 541 detectable detectable JJ 542 544 in in IN 545 554 untreated untreated JJ 555 560 HL-60 hl-60 NN 561 569 leukemic leukemic JJ 570 575 cells cell NNS 575 576 , , , 577 586 increased increase VBD 587 600 significantly significantly RB 601 603 by by IN 604 605 6 6 CD 606 607 h h NN 607 608 , , , 609 612 and and CC 613 620 reached reach VBD 621 625 near near IN 626 633 maximal maximal JJ 634 640 levels level NNS 641 643 by by IN 644 646 24 24 CD 647 648 h h NN 649 651 of of IN 652 660 exposure exposure NN 661 663 to to TO 664 666 32 32 CD 667 669 nM nM NNP 670 673 TPA TPA NNP 673 674 . . . 675 682 Similar similar JJ 683 691 kinetics kinetic NNS 692 694 of of IN 695 700 c-jun c-jun NN 701 710 induction induction NN 711 713 by by IN 714 717 TPA TPA NNP 718 722 were be VBD 723 731 observed observe VBN 732 734 in in IN 735 740 human human JJ 741 746 U-937 u-937 NN 747 750 and and CC 751 756 THP-1 thp-1 NN 757 766 monocytic monocytic JJ 767 775 leukemia leukemia NN 776 781 cells cell NNS 781 782 . . . 783 790 Similar similar JJ 791 799 findings finding NNS 800 804 were be VBD 805 813 obtained obtain VBN 814 818 with with IN 819 829 bryostatin bryostatin NN 830 831 1 1 CD 832 833 ( ( NN 833 835 10 10 CD 836 838 nM nM NNP 838 839 ) ) ) 839 840 , , , 841 848 another another DT 849 858 activator activator NN 859 861 of of IN 862 869 protein protein NN 870 876 kinase kinase NNP 877 878 C C NNP 879 882 and and CC 883 890 inducer inducer NN 891 893 of of IN 894 903 monocytic monocytic JJ 904 919 differentiation differentiation NN 919 920 . . . 921 932 Furthermore furthermore RB 932 933 , , , 934 955 1,25-dihydroxyvitamin 1,25-dihydroxyvitamin NN 956 958 D3 d3 NN 959 960 ( ( ( 960 963 0.5 0.5 CD 964 970 microM microM NNP 970 971 ) ) ) 971 972 , , , 973 974 a a DT 975 987 structurally structurally RB 988 996 distinct distinct JJ 997 1002 agent agent NN 1003 1008 which which WDT 1009 1013 also also RB 1014 1021 induces induce VBZ 1022 1027 HL-60 HL-60 NNP 1028 1037 monocytic monocytic JJ 1038 1053 differentiation differentiation NN 1053 1054 , , , 1055 1064 increased increase VBD 1065 1070 c-jun c-jun NN 1071 1081 expression expression NN 1081 1082 . . . 1083 1086 TPA TPA NNP 1087 1096 treatment treatment NN 1097 1099 of of IN 1100 1105 HL-60 hl-60 NN 1106 1111 cells cell NNS 1112 1114 in in IN 1115 1118 the the DT 1119 1127 presence presence NN 1128 1130 of of IN 1131 1144 cycloheximide cycloheximide NN 1145 1148 was be VBD 1149 1159 associated associate VBN 1160 1164 with with IN 1165 1179 superinduction superinduction NN 1180 1182 of of IN 1183 1188 c-jun c-jun NN 1189 1200 transcripts transcript NNS 1200 1201 . . . 1202 1208 Run-on run-on JJ 1209 1217 analysis analysis NN 1218 1230 demonstrated demonstrate VBD 1231 1241 detectable detectable JJ 1242 1248 levels level NNS 1249 1251 of of IN 1252 1257 c-jun c-jun NN 1258 1262 gene gene NN 1263 1276 transcription transcription NN 1277 1279 in in IN 1280 1289 untreated untreated JJ 1290 1295 HL-60 hl-60 NN 1296 1301 cells cell NNS 1301 1302 , , , 1303 1306 and and CC 1307 1311 that that IN 1312 1320 exposure exposure NN 1321 1323 to to TO 1324 1327 TPA TPA NNP 1328 1337 increases increase VBZ 1338 1342 this this DT 1343 1347 rate rate NN 1348 1356 3.3-fold 3.3-fold RB 1356 1357 . . . 1358 1367 Treatment Treatment NNP 1368 1370 of of IN 1371 1376 HL-60 HL-60 NNP 1377 1382 cells cell NNS 1383 1387 with with IN 1388 1392 both both CC 1393 1396 TPA TPA NNP 1397 1400 and and CC 1401 1414 cycloheximide cycloheximide NN 1415 1418 had have VBD 1419 1421 no no DT 1422 1428 effect effect NN 1429 1431 on on IN 1432 1435 the the DT 1436 1441 rates rate NNS 1442 1444 of of IN 1445 1450 c-jun c-jun NN 1451 1464 transcription transcription NN 1464 1465 . . . 1466 1469 The the DT 1470 1479 half-life half-life NN 1480 1482 of of IN 1483 1488 c-jun c-jun NN 1489 1492 RNA RNA NNP 1493 1495 as as IN 1496 1506 determined determine VBN 1507 1509 by by IN 1510 1518 treating treat VBG 1519 1524 HL-60 hl-60 NN 1525 1530 cells cell NNS 1531 1535 with with IN 1536 1539 TPA TPA NNP 1540 1543 and and CC 1544 1555 actinomycin actinomycin NNP 1556 1557 D D NNP 1558 1561 was be VBD 1562 1564 30 30 CD 1565 1568 min min NN 1568 1569 . . . 1570 1572 In in IN 1573 1581 contrast contrast NN 1581 1582 , , , 1583 1586 the the DT 1587 1596 half-life half-life NN 1597 1599 of of IN 1600 1605 c-jun c-jun NN 1606 1609 RNA RNA NNP 1610 1612 in in IN 1613 1624 TPA-treated tpa-treated JJ 1625 1630 HL-60 hl-60 NN 1631 1636 cells cell NNS 1637 1644 exposed expose VBN 1645 1647 to to TO 1648 1661 cycloheximide cycloheximide NN 1662 1665 and and CC 1666 1677 actinomycin actinomycin NN 1678 1679 D D NNP 1680 1683 was be VBD 1684 1691 greater great JJR 1692 1696 than than IN 1697 1698 2 2 CD 1699 1700 h h NN 1700 1701 . . . 1702 1707 These these DT 1708 1716 findings finding NNS 1717 1726 suggested suggest VBD 1727 1731 that that IN 1732 1735 the the DT 1736 1744 increase increase NN 1745 1747 in in IN 1748 1753 c-jun c-jun NN 1754 1757 RNA RNA NNP 1758 1766 observed observe VBN 1767 1773 during during IN 1774 1785 TPA-induced tpa-induced JJ 1786 1795 monocytic monocytic JJ 1796 1811 differentiation differentiation NN 1812 1814 is be VBZ 1815 1823 mediated mediate VBN 1824 1826 by by IN 1827 1831 both both CC 1832 1847 transcriptional transcriptional JJ 1848 1851 and and CC 1852 1872 post-transcriptional post-transcriptional JJ 1873 1883 mechanisms mechanism NNS 1883 1884 . . .