0 8 Distinct distinct JJ 9 14 roles role NNS 15 17 of of IN 18 21 the the DT 22 31 molecular molecular JJ 32 41 chaperone chaperone NN 42 47 hsp90 hsp90 NN 48 50 in in IN 51 61 modulating modulate VBG 62 68 dioxin dioxin NN 69 77 receptor receptor NN 78 86 function function NN 87 90 via via IN 91 94 the the DT 95 100 basic basic JJ 101 117 helix-loop-helix helix-loop-helix JJ 118 121 and and CC 122 125 PAS PAS NNP 126 133 domains domain NNS 133 134 . . . 136 139 The the DT 140 153 intracellular intracellular JJ 154 160 dioxin dioxin NN 161 169 receptor receptor NN 170 178 mediates mediate VBZ 179 185 signal signal NN 186 198 transduction transduction NN 199 201 by by IN 202 208 dioxin dioxin NN 209 212 and and CC 213 222 functions function VBZ 223 225 as as IN 226 227 a a DT 228 244 ligand-activated ligand-activated JJ 245 258 transcription transcription NN 259 265 factor factor NN 265 266 . . . 267 269 It it PRP 270 278 contains contain VBZ 279 280 a a DT 281 286 basic basic JJ 287 303 helix-loop-helix helix-loop-helix JJ 304 305 ( ( ( 305 309 bHLH bhlh JJ 309 310 ) ) ) 311 316 motif motif NN 317 327 contiguous contiguous JJ 328 332 with with IN 333 334 a a DT 335 347 Per-Arnt-Sim Per-Arnt-Sim NNP 348 349 ( ( ( 349 352 PAS PAS NNP 352 353 ) ) ) 354 362 homology homology NN 363 369 region region NN 369 370 . . . 371 373 In in IN 374 382 extracts extract NNS 383 387 from from IN 388 401 nonstimulated nonstimulated JJ 402 407 cells cell NNS 408 411 the the DT 412 420 receptor receptor NN 421 423 is be VBZ 424 433 recovered recover VBN 434 436 in in IN 437 439 an an DT 440 449 inducible inducible JJ 450 461 cytoplasmic cytoplasmic JJ 462 466 form form NN 467 477 associated associate VBN 478 482 with with IN 483 486 the the DT 487 493 90-kDa 90-kda JJ 494 498 heat heat NN 499 504 shock shock NN 505 512 protein protein NN 513 514 ( ( ( 514 519 hsp90 hsp90 NN 519 520 ) ) ) 520 521 , , , 522 523 a a DT 524 533 molecular molecular JJ 534 543 chaperone chaperone NN 543 544 . . . 545 547 We we PRP 548 552 have have VBP 553 566 reconstituted reconstitute VBN 567 583 ligand-dependent ligand-dependent JJ 584 594 activation activation NN 595 597 of of IN 598 601 the the DT 602 610 receptor receptor NN 611 613 to to TO 614 615 a a DT 616 627 DNA-binding dna-binding JJ 628 632 form form NN 633 635 by by IN 636 641 using use VBG 642 645 the the DT 646 652 dioxin dioxin NN 653 661 receptor receptor NN 662 665 and and CC 666 669 its its PRP$ 670 678 bHLH-PAS bhlh-pas JJ 679 686 partner partner NN 687 693 factor factor NN 694 698 Arnt Arnt NNP 699 708 expressed express VBN 709 711 by by IN 712 714 in in FW 715 720 vitro vitro FW 721 732 translation translation NN 733 735 in in IN 736 748 reticulocyte reticulocyte NN 749 755 lysate lysate NN 755 756 . . . 757 765 Deletion deletion NN 766 768 of of IN 769 772 the the DT 773 776 PAS PAS NNP 777 783 domain domain NN 784 786 of of IN 787 790 the the DT 791 799 receptor receptor NN 800 808 resulted result VBD 809 811 in in IN 812 824 constitutive constitutive JJ 825 837 dimerization dimerization NN 838 842 with with IN 843 847 Arnt Arnt NNP 847 848 . . . 849 851 In in IN 852 860 contrast contrast NN 860 861 , , , 862 866 this this DT 867 875 receptor receptor NN 876 882 mutant mutant NN 883 889 showed show VBD 890 893 low low JJ 894 900 levels level NNS 901 903 of of IN 904 914 xenobiotic xenobiotic JJ 915 923 response response NN 924 939 element-binding element-binding JJ 940 948 activity activity NN 948 949 , , , 950 960 indicating indicate VBG 961 965 that that IN 966 969 the the DT 970 973 PAS PAS NNP 974 980 domain domain NN 981 984 may may MD 985 987 be be VB 988 997 important important JJ 998 1001 for for IN 1002 1013 DNA-binding dna-binding JJ 1014 1022 affinity affinity NN 1023 1029 and/or and/or CC 1030 1041 specificity specificity NN 1042 1044 of of IN 1045 1048 the the DT 1049 1057 receptor receptor NN 1057 1058 . . . 1059 1061 It it PRP 1062 1065 was be VBD 1066 1069 not not RB 1070 1078 possible possible JJ 1079 1081 to to TO 1082 1094 reconstitute reconstitute VB 1095 1101 dioxin dioxin NN 1102 1110 receptor receptor NN 1111 1119 function function NN 1120 1124 with with IN 1125 1133 proteins protein NNS 1134 1143 expressed express VBN 1144 1146 in in IN 1147 1152 wheat wheat NN 1153 1157 germ germ NN 1158 1164 lysate lysate NN 1164 1165 . . . 1166 1168 In in IN 1169 1173 line line NN 1174 1178 with with IN 1179 1184 these these DT 1185 1197 observations observation NNS 1197 1198 , , , 1199 1211 reticulocyte reticulocyte NN 1212 1218 lysate lysate NN 1219 1222 but but CC 1223 1226 not not RB 1227 1232 wheat wheat NN 1233 1237 germ germ NN 1238 1244 lysate lysate NN 1245 1253 promoted promote VBD 1254 1257 the the DT 1258 1269 association association NN 1270 1272 of of IN 1273 1275 de de FW 1276 1280 novo novo FW 1281 1292 synthesized synthesize VBN 1293 1299 dioxin dioxin NN 1300 1308 receptor receptor NN 1309 1313 with with IN 1314 1319 hsp90 hsp90 NN 1319 1320 . . . 1321 1323 At at IN 1324 1329 least least JJS 1330 1333 two two CD 1334 1342 distinct distinct JJ 1343 1350 domains domain NNS 1351 1353 of of IN 1354 1357 the the DT 1358 1366 receptor receptor NN 1367 1375 mediated mediated JJ 1376 1387 interaction interaction NN 1388 1392 with with IN 1393 1398 hsp90 hsp90 NN 1398 1399 : : : 1400 1403 the the DT 1404 1418 ligand-binding ligand-binding JJ 1419 1425 domain domain NN 1426 1433 located located JJ 1434 1440 within within IN 1441 1444 the the DT 1445 1448 PAS PAS NNP 1449 1455 region region NN 1456 1459 and and CC 1459 1460 , , , 1461 1473 surprisingly surprisingly RB 1473 1474 , , , 1475 1478 the the DT 1479 1483 bHLH bhlh JJ 1484 1490 domain domain NN 1490 1491 . . . 1492 1499 Whereas whereas IN 1500 1514 ligand-binding ligand-binding JJ 1515 1523 activity activity NN 1524 1534 correlated correlate VBD 1535 1539 with with IN 1540 1551 association association NN 1552 1556 with with IN 1557 1562 hsp90 hsp90 NN 1562 1563 , , , 1564 1574 bHLH-hsp90 bhlh-hsp90 NN 1575 1586 interaction interaction NN 1587 1595 appeared appear VBD 1596 1598 to to TO 1599 1601 be be VB 1602 1611 important important JJ 1612 1615 for for IN 1616 1627 DNA-binding dna-binding JJ 1628 1636 activity activity NN 1637 1640 but but CC 1641 1644 not not RB 1645 1648 for for IN 1649 1661 dimerization dimerization NN 1662 1664 of of IN 1665 1668 the the DT 1669 1677 receptor receptor NN 1677 1678 . . . 1679 1686 Several several JJ 1687 1695 distinct distinct JJ 1696 1701 roles role NNS 1702 1705 for for IN 1706 1711 hsp90 hsp90 NN 1712 1714 in in IN 1715 1725 modulating modulate VBG 1726 1732 dioxin dioxin NN 1733 1741 receptor receptor NN 1742 1750 function function NN 1751 1754 are be VBP 1755 1764 therefore therefore RB 1765 1771 likely likely JJ 1771 1772 : : : 1773 1780 correct correct JJ 1781 1788 folding folding NN 1789 1791 of of IN 1792 1795 the the DT 1796 1810 ligand-binding ligand-binding JJ 1811 1817 domain domain NN 1817 1818 , , , 1819 1831 interference interference NN 1832 1836 with with IN 1837 1841 Arnt Arnt NNP 1842 1860 heterodimerization heterodimerization NN 1860 1861 , , , 1862 1865 and and CC 1866 1873 folding folding NN 1874 1876 of of IN 1877 1878 a a DT 1879 1890 DNA-binding dna-binding JJ 1891 1903 conformation conformation NN 1904 1906 of of IN 1907 1910 the the DT 1911 1915 bHLH bhlh JJ 1916 1922 domain domain NN 1922 1923 . . . 1924 1928 Thus thus RB 1928 1929 , , , 1930 1933 the the DT 1934 1940 dioxin dioxin NN 1941 1949 receptor receptor NN 1950 1956 system system NN 1957 1965 provides provide VBZ 1966 1967 a a DT 1968 1975 complex complex JJ 1976 1979 and and CC 1980 1991 interesting interesting JJ 1992 1997 model model NN 1998 2000 of of IN 2001 2004 the the DT 2005 2015 regulation regulation NN 2016 2018 of of IN 2019 2032 transcription transcription NN 2033 2040 factors factor NNS 2041 2043 by by IN 2044 2049 hsp90 hsp90 NN 2049 2050 . . .