0 10 Regulation regulation NN 11 13 of of IN 14 19 c-jun c-jun NN 20 30 expression expression NN 31 37 during during IN 38 47 induction induction NN 48 50 of of IN 51 60 monocytic monocytic JJ 61 76 differentiation differentiation NN 77 79 by by IN 80 87 okadaic okadaic JJ 88 92 acid acid NN 92 93 . . . 95 98 The the DT 99 106 present present JJ 107 111 work work NN 112 115 has have VBZ 116 124 examined examine VBN 125 128 the the DT 129 136 effects effect NNS 137 139 of of IN 140 147 okadaic okadaic JJ 148 152 acid acid NN 152 153 , , , 154 156 an an DT 157 166 inhibitor inhibitor NN 167 169 of of IN 170 174 type type NN 175 176 1 1 CD 177 180 and and CC 181 183 2A 2a NN 184 191 protein protein NN 192 204 phosphatases phosphatas NNS 204 205 , , , 206 208 on on IN 209 212 the the DT 213 223 regulation regulation NN 224 226 of of IN 227 232 c-jun c-jun NN 233 243 expression expression NN 244 250 during during IN 251 260 monocytic monocytic JJ 261 276 differentiation differentiation NN 277 279 of of IN 280 285 U-937 u-937 NN 286 294 leukemia leukemia NN 295 300 cells cell NNS 300 301 . . . 302 305 The the DT 306 313 results result NNS 314 325 demonstrate demonstrate VBP 326 330 that that IN 331 338 okadaic okadaic JJ 339 343 acid acid NN 344 353 treatment treatment NN 354 356 is be VBZ 357 367 associated associate VBN 368 372 with with IN 373 382 induction induction NN 383 385 of of IN 386 387 a a DT 388 402 differentiated differentiate VBN 403 411 monocyte monocyte NN 412 421 phenotype phenotype NN 422 435 characterized characterize VBN 436 438 by by IN 438 439 : : : 440 441 ( ( ( 441 442 a a LS 442 443 ) ) ) 444 450 growth growth NN 451 457 arrest arrest NN 457 458 ; ; : 459 460 ( ( ( 460 461 b b LS 461 462 ) ) ) 463 472 increases increase NNS 473 475 in in IN 476 481 Mac-1 mac-1 NN 482 486 cell cell NN 487 494 surface surface NN 495 502 antigen antigen NN 503 513 expression expression NN 513 514 ; ; : 515 516 ( ( ( 516 517 c c LS 517 518 ) ) ) 519 534 down-regulation down-regulation NN 535 537 of of IN 538 543 c-myc c-myc NN 544 555 transcripts transcript NNS 555 556 ; ; : 557 560 and and CC 561 562 ( ( ( 562 563 d d LS 563 564 ) ) ) 565 574 induction induction NN 575 577 of of IN 578 583 tumor tumor NN 584 592 necrosis necrosis NN 593 599 factor factor NN 600 604 gene gene NN 605 615 expression expression NN 615 616 . . . 617 621 This this DT 622 631 induction induction NN 632 634 of of IN 635 644 monocytic monocytic JJ 645 660 differentiation differentiation NN 661 664 was be VBD 665 675 associated associate VBN 676 680 with with IN 681 690 transient transient JJ 691 700 increases increase NNS 701 703 in in IN 704 709 c-jun c-jun NN 710 714 mRNA mrna NN 715 721 levels level NNS 721 722 , , , 723 728 which which WDT 729 733 were be VBD 734 741 maximal maximal JJ 742 744 at at IN 745 746 6 6 CD 747 749 h. h. NN 750 757 Similar similar JJ 758 765 effects effect NNS 766 770 were be VBD 771 779 obtained obtain VBN 780 783 for for IN 784 787 the the DT 788 793 c-fos c-fos NN 794 798 gene gene NN 798 799 . . . 800 806 Run-on run-on JJ 807 815 analysis analysis NN 816 828 demonstrated demonstrate VBD 829 839 detectable detectable JJ 840 846 levels level NNS 847 849 of of IN 850 855 c-jun c-jun NN 856 869 transcription transcription NN 870 872 in in IN 873 878 U-937 u-937 NN 879 884 cells cell NNS 885 888 and and CC 889 893 that that IN 894 898 this this DT 899 903 rate rate NN 904 906 is be VBZ 907 916 increased increase VBN 917 930 approximately approximately RB 931 938 40-fold 40-fold RB 939 948 following follow VBG 949 956 okadaic okadaic JJ 957 961 acid acid NN 962 971 exposure. exposure. NN 972 977 c-jun c-jun NN 978 982 mRNA mrna NN 983 989 levels level NNS 990 994 were be VBD 995 1007 superinduced superinduce VBN 1008 1010 in in IN 1011 1016 cells cell NNS 1017 1024 treated treat VBN 1025 1029 with with IN 1030 1034 both both CC 1035 1042 okadaic okadaic JJ 1043 1047 acid acid NN 1048 1051 and and CC 1052 1065 cycloheximide cycloheximide NN 1065 1066 , , , 1067 1074 whereas whereas IN 1075 1085 inhibition inhibition NN 1086 1088 of of IN 1089 1096 protein protein NN 1097 1106 synthesis synthesis NN 1107 1110 had have VBD 1111 1117 little little JJ 1117 1118 , , , 1119 1121 if if IN 1122 1125 any any DT 1125 1126 , , , 1127 1133 effect effect NN 1134 1136 on on IN 1137 1144 okadaic okadaic JJ 1145 1157 acid-induced acid-induced JJ 1158 1163 c-jun c-jun NN 1164 1177 transcription transcription NN 1177 1178 . . . 1179 1182 The the DT 1183 1192 half-life half-life NN 1193 1195 of of IN 1196 1201 c-jun c-jun NN 1202 1206 mRNA mRNA NNP 1207 1210 was be VBD 1211 1218 similar similar JJ 1219 1220 ( ( ( 1220 1225 45-50 45-50 CD 1226 1229 min min NN 1229 1230 ) ) ) 1231 1233 in in IN 1234 1238 both both CC 1239 1248 untreated untreated JJ 1249 1252 and and CC 1253 1260 okadaic okadaic JJ 1261 1273 acid-induced acid-induced JJ 1274 1279 cells cell NNS 1279 1280 . . . 1281 1283 In in IN 1284 1292 contrast contrast NN 1292 1293 , , , 1294 1303 treatment treatment NN 1304 1308 with with IN 1309 1313 both both CC 1314 1321 okadaic okadaic JJ 1322 1326 acid acid NN 1327 1330 and and CC 1331 1344 cycloheximide cycloheximide NN 1345 1348 was be VBD 1349 1359 associated associate VBN 1360 1364 with with IN 1365 1378 stabilization stabilization NN 1379 1380 ( ( ( 1380 1381 t t NN 1382 1385 1/2 1/2 CD 1386 1387 = = SYM 1388 1390 90 90 CD 1391 1394 min min NN 1394 1395 ) ) ) 1396 1398 of of IN 1399 1404 c-jun c-jun NN 1405 1416 transcripts transcript NNS 1416 1417 . . . 1418 1423 Taken take VBN 1424 1432 together together RB 1432 1433 , , , 1434 1439 these these DT 1440 1448 findings finding NNS 1449 1457 indicate indicate VBP 1458 1462 that that IN 1463 1466 the the DT 1467 1476 induction induction NN 1477 1479 of of IN 1480 1485 c-jun c-jun NN 1486 1499 transcription transcription NN 1500 1502 by by IN 1503 1510 okadaic okadaic JJ 1511 1515 acid acid NN 1516 1518 is be VBZ 1519 1529 controlled control VBN 1530 1539 primarily primarily RB 1540 1542 by by IN 1543 1544 a a DT 1545 1560 transcriptional transcriptional JJ 1561 1570 mechanism mechanism NN 1570 1571 . . . 1572 1577 Since since IN 1578 1586 previous previous JJ 1587 1594 studies study NNS 1595 1599 have have VBP 1600 1612 demonstrated demonstrate VBN 1613 1617 that that IN 1618 1621 the the DT 1622 1627 c-jun c-jun NN 1628 1632 gene gene NN 1633 1635 is be VBZ 1636 1647 autoinduced autoinduce VBN 1648 1650 by by IN 1651 1659 Jun/AP-1 jun/ap-1 NN 1659 1660 , , , 1661 1663 we we PRP 1664 1668 also also RB 1669 1676 studied study VBD 1677 1690 transcription transcription NN 1691 1693 of of IN 1694 1699 c-jun c-jun NN 1700 1708 promoter promoter NN 1709 1710 ( ( ( 1710 1719 positions position NNS 1720 1739 -132/+170)-reporter -132/+170)-reporter NN 1740 1744 gene gene NN 1745 1755 constructs construct NNS 1756 1760 with with IN 1761 1764 and and CC 1765 1772 without without IN 1773 1774 a a DT 1775 1782 mutated mutate VBN 1783 1787 AP-1 ap-1 NN 1788 1795 element element NN 1795 1796 . . . 1797 1798 ( ( ( 1798 1806 ABSTRACT abstract NN 1807 1816 TRUNCATED truncated VBN 1817 1819 AT at IN 1820 1823 250 250 CD 1824 1829 WORDS words NNS 1829 1830 ) ) )