0 15 Transcriptional transcriptional JJ 16 23 control control NN 24 26 of of IN 27 44 steroid-regulated steroid-regulated JJ 45 54 apoptosis apoptosis NN 55 57 in in IN 58 64 murine murine JJ 65 72 thymoma thymoma NN 73 78 cells cell NNS 78 79 . . . 81 86 Early early JJ 87 94 studies study NNS 95 97 in in IN 98 104 murine murine JJ 105 106 T t NN 107 111 cell cell NN 112 117 lines line NNS 118 127 indicated indicate VBD 128 132 that that IN 133 148 transcriptional transcriptional JJ 149 164 transactivation transactivation NN 165 174 functions function NNS 175 182 encoded encode VBN 183 185 in in IN 186 189 the the DT 190 204 glucocorticoid glucocorticoid NN 205 213 receptor receptor NN 214 215 ( ( ( 215 217 GR GR NNP 217 218 ) ) ) 219 229 N-terminal n-terminal JJ 230 236 domain domain NN 237 240 are be VBP 241 249 required require VBN 250 253 for for IN 254 277 glucocorticoid-mediated glucocorticoid-mediated JJ 278 287 apoptosis apoptosis NN 287 288 . . . 289 296 However however RB 296 297 , , , 298 302 more more RBR 303 309 recent recent JJ 310 317 studies study NNS 318 320 in in IN 321 326 human human JJ 327 328 T t NN 329 333 cell cell NN 334 339 lines line NNS 340 344 have have VBP 345 354 suggested suggest VBN 355 359 that that IN 360 363 the the DT 364 374 N-terminal n-terminal JJ 375 381 domain domain NN 382 384 is be VBZ 385 388 not not RB 389 398 necessary necessary JJ 399 402 for for IN 403 420 steroid-regulated steroid-regulated JJ 421 430 apoptosis apoptosis NN 431 434 and and CC 435 439 that that IN 440 451 GR-mediated gr-mediated JJ 452 467 transrepression transrepression NN 468 471 may may MD 472 474 be be VB 475 478 the the DT 479 483 more more RBR 484 492 critical critical JJ 493 502 mechanism mechanism NN 502 503 . . . 504 506 To to TO 507 513 better well RBR 514 524 understand understand VB 525 528 the the DT 529 541 contribution contribution NN 542 544 of of IN 545 548 the the DT 549 551 GR GR NNP 552 562 N-terminal n-terminal JJ 563 578 transactivation transactivation NN 579 585 domain domain NN 586 588 in in IN 589 598 mediating mediate VBG 599 605 murine murine JJ 606 615 thymocyte thymocyte NN 616 625 apoptosis apoptosis NN 625 626 , , , 627 629 we we PRP 630 636 stably stably RB 637 648 transfected transfecte VBD 649 651 GR GR NNP 651 652 , , , 653 655 GR GR NNP 656 664 variants variant NNS 664 665 , , , 666 669 and and CC 670 673 the the DT 674 682 androgen androgen NN 683 691 receptor receptor NN 692 693 ( ( ( 693 695 AR AR NNP 695 696 ) ) ) 697 701 into into IN 702 719 receptor-negative receptor-negative JJ 720 723 S49 S49 NNP 724 730 murine murine JJ 731 738 thymoma thymoma NN 739 744 cells cell NNS 744 745 . . . 746 748 GR GR NNP 749 759 expression expression NN 760 766 levels level NNS 767 771 were be VBD 772 777 shown show VBN 778 780 to to TO 781 783 be be VB 784 797 rate-limiting rate-limiting JJ 798 801 for for IN 802 812 initiating initiate VBG 813 816 the the DT 817 826 apoptotic apoptotic JJ 827 834 pathway pathway NN 834 835 , , , 836 839 and and CC 840 841 a a DT 842 850 positive positive JJ 851 862 correlation correlation NN 863 870 between between IN 871 878 steroid steroid NN 879 890 sensitivity sensitivity NN 891 894 and and CC 895 906 GR-mediated gr-mediated JJ 907 916 induction induction NN 917 919 of of IN 920 922 an an DT 923 933 integrated integrate VBN 934 939 mouse mouse NN 940 947 mammary mammary JJ 948 953 tumor tumor NN 954 959 virus virus NN 960 961 ( ( ( 961 965 MMTV MMTV NNP 965 966 ) ) ) 967 970 LTR LTR NNP 971 979 reporter reporter NN 980 984 gene gene NN 985 988 was be VBD 989 997 observed observe VBN 997 998 . . . 999 1007 Analysis Analysis NNP 1008 1010 of of IN 1011 1013 GR GR NNP 1014 1022 chimeric chimeric JJ 1023 1032 receptors receptor NNS 1033 1043 containing contain VBG 1044 1047 the the DT 1048 1054 potent potent JJ 1055 1059 VP16 vp16 NN 1060 1063 and and CC 1064 1067 E1A E1A NNP 1068 1073 viral viral JJ 1074 1089 transactivation transactivation NN 1090 1097 domains domain NNS 1098 1100 in in IN 1101 1106 place place NN 1107 1109 of of IN 1110 1113 the the DT 1114 1116 GR GR NNP 1117 1118 N N NNP 1119 1127 terminus terminus NNP 1128 1136 revealed reveal VBD 1137 1141 that that IN 1142 1146 even even RB 1147 1150 low low JJ 1151 1156 level level NN 1157 1167 expression expression NN 1168 1170 of of IN 1171 1176 these these DT 1177 1186 receptors receptor NNS 1187 1195 resulted result VBD 1196 1198 in in IN 1199 1203 both both DT 1204 1212 enhanced enhance VBD 1213 1220 steroid steroid NN 1221 1232 sensitivity sensitivity NN 1233 1236 and and CC 1237 1241 MMTV MMTV NNP 1242 1251 induction induction NN 1251 1252 , , , 1253 1257 thus thus RB 1258 1268 supporting support VBG 1269 1270 a a DT 1271 1275 role role NN 1276 1279 for for IN 1280 1295 transactivation transactivation NN 1296 1298 in in IN 1299 1308 apoptosis apoptosis NN 1308 1309 . . . 1310 1312 In in IN 1313 1321 contrast contrast NN 1321 1322 , , , 1323 1325 we we PRP 1326 1331 found find VBD 1332 1336 that that IN 1337 1339 AR ar NN 1340 1343 can can MD 1344 1352 initiate initiate VB 1353 1362 apoptosis apoptosis NN 1363 1365 in in IN 1366 1369 S49 s49 NN 1370 1375 cells cell NNS 1376 1381 after after IN 1382 1391 treatment treatment NN 1392 1396 with with IN 1397 1398 5 5 CD 1399 1424 alpha-dihydrotestosterone alpha-dihydrotestosterone NN 1424 1425 , , , 1426 1433 despite despite IN 1434 1437 its its PRP$ 1438 1446 relative relative JJ 1447 1456 inability inability NN 1457 1459 to to TO 1460 1466 induce induce VB 1467 1471 high high JJ 1472 1477 level level NN 1478 1488 expression expression NN 1489 1491 of of IN 1492 1496 MMTV MMTV NNP 1496 1497 . . . 1498 1500 To to TO 1501 1512 investigate investigate VB 1513 1517 this this DT 1518 1525 further further RBR 1525 1526 , , , 1527 1529 we we PRP 1530 1538 examined examine VBD 1539 1542 the the DT 1543 1560 steroid-regulated steroid-regulated JJ 1561 1571 expression expression NN 1572 1574 of of IN 1575 1577 an an DT 1578 1588 endogenous endogenous JJ 1589 1607 thymocyte-specific thymocyte-specific JJ 1608 1612 gene gene NN 1613 1619 called call VBN 1620 1625 GIG18 gig18 NN 1625 1626 . . . 1627 1629 We we PRP 1630 1635 found find VBD 1636 1640 that that IN 1641 1646 GIG18 gig18 NN 1647 1650 was be VBD 1651 1658 rapidly rapidly RB 1659 1666 induced induce VBN 1667 1669 to to TO 1670 1680 comparable comparable JJ 1681 1687 levels level NNS 1688 1690 by by IN 1691 1695 both both CC 1696 1698 AR AR NNP 1699 1702 and and CC 1703 1705 GR GR NNP 1705 1706 , , , 1707 1720 demonstrating demonstrate VBG 1721 1725 that that IN 1726 1728 AR ar NN 1729 1732 can can MD 1733 1739 indeed indeed RB 1740 1748 function function VB 1749 1751 as as IN 1752 1753 a a DT 1754 1769 transcriptional transcriptional JJ 1770 1779 activator activator NN 1780 1782 in in IN 1783 1786 S49 s49 NN 1787 1792 cells cell NNS 1793 1796 and and CC 1796 1797 , , , 1798 1806 moreover moreover RB 1806 1807 , , , 1808 1812 that that IN 1813 1818 GIG18 gig18 NN 1819 1828 induction induction NN 1829 1832 may may MD 1833 1835 be be VB 1836 1837 a a DT 1838 1844 marker marker NN 1845 1847 of of IN 1848 1853 early early JJ 1854 1863 apoptotic apoptotic JJ 1864 1870 events event NNS 1871 1873 in in IN 1874 1889 steroid-treated steroid-treated JJ 1890 1895 cells cell NNS 1895 1896 . . . 1897 1902 Taken take VBN 1903 1911 together together RB 1911 1912 , , , 1913 1918 these these DT 1919 1926 results result NNS 1927 1934 support support VBP 1935 1938 our our PRP$ 1939 1949 conclusion conclusion NN 1950 1954 that that IN 1955 1970 transcriptional transcriptional JJ 1971 1986 transactivation transactivation NN 1987 1989 is be VBZ 1990 1991 a a DT 1992 2001 necessary necessary JJ 2002 2011 signaling signaling NN 2012 2021 component component NN 2022 2024 of of IN 2025 2028 S49 S49 NNP 2029 2033 cell cell NN 2034 2043 apoptosis apoptosis NN 2043 2044 , , , 2045 2053 although although IN 2054 2056 an an DT 2057 2067 additional additional JJ 2068 2072 role role NN 2073 2076 for for IN 2077 2088 GR-mediated gr-mediated JJ 2089 2104 transrepression transrepression NN 2105 2111 cannot cannot MD 2112 2114 be be VB 2115 2123 excluded exclude VBN 2123 2124 . . .