0 10 Regulation Regulation NNP 11 13 of of IN 14 22 NF-kappa NF-kappa NNP 23 24 B B NNP 25 33 activity activity NN 34 36 by by IN 37 38 I i NN 39 44 kappa kappa NN 45 46 B B NNP 47 52 alpha alpha NN 53 56 and and CC 57 58 I i NN 59 64 kappa kappa NN 65 66 B B NNP 67 71 beta beta NN 72 81 stability stability NN 81 82 . . . 84 97 Transcription Transcription NNP 98 104 factor factor NN 105 113 NF-kappa NF-kappa NNP 114 115 B B NNP 116 120 must must MD 121 123 be be VB 124 132 released release VBN 133 137 from from IN 138 149 cytoplasmic cytoplasmic JJ 150 160 inhibitory inhibitory JJ 161 170 molecules molecule NNS 171 172 ( ( ( 172 173 I i NN 174 179 kappa kappa NN 180 182 Bs b NNS 182 183 ) ) ) 184 186 in in IN 187 192 order order NN 193 195 to to TO 196 200 move move VB 201 203 to to TO 204 207 the the DT 208 215 nucleus nucleus NN 216 219 and and CC 220 222 to to TO 223 231 activate activate VB 232 235 its its PRP$ 236 242 target target NN 243 248 genes gene NNS 248 249 . . . 250 256 Little little JJ 257 259 is be VBZ 260 265 known know VBN 266 271 about about IN 272 275 the the DT 276 286 mechanisms mechanism NNS 287 297 regulating regulate VBG 298 301 the the DT 302 313 maintenance maintenance NN 314 316 of of IN 317 329 constitutive constitutive JJ 330 337 nuclear nuclear JJ 338 346 NF-kappa NF-kappa NNP 347 348 B B NNP 349 351 in in IN 352 356 some some DT 357 367 cell-types cell-type NNS 368 371 and and CC 372 374 of of IN 375 384 sustained sustained JJ 385 392 nuclear nuclear JJ 393 401 NF-kappa NF-kappa NNP 402 403 B B NNP 404 412 activity activity NN 413 418 after after IN 419 430 stimulation stimulation NN 430 431 . . . 432 441 Increased increase VBN 442 450 turnover turnover NN 451 454 has have VBZ 455 459 been be VBN 460 470 implicated implicate VBN 471 473 in in IN 474 477 the the DT 478 488 regulation regulation NN 489 491 of of IN 492 504 constitutive constitutive JJ 505 513 NF-kappa NF-kappa NNP 514 515 B B NNP 516 524 activity activity NN 525 527 in in IN 528 534 mature mature JJ 535 536 B B NNP 537 542 cells cell NNS 542 543 . . . 544 546 We we PRP 547 556 therefore therefore RB 557 565 compared compare VBD 566 569 the the DT 570 578 turnover turnover NN 579 581 of of IN 582 583 I i NN 584 589 kappa kappa NN 590 591 B B NNP 592 597 alpha alpha NN 598 601 and and CC 602 603 I i NN 604 609 kappa kappa NN 610 611 B B NNP 612 616 beta beta NN 617 619 in in IN 620 626 mature mature JJ 627 628 B B NNP 629 634 cells cell NNS 635 638 and and CC 639 643 HeLa HeLa NNP 644 649 cells cell NNS 649 650 . . . 651 655 Both both DT 656 664 proteins protein NNS 665 672 display display VBP 673 674 a a DT 675 679 high high JJ 680 688 turnover turnover NN 689 691 in in IN 692 693 B B NNP 694 699 cells cell NNS 700 708 although although IN 709 710 I i NN 711 716 kappa kappa NN 717 718 B B NNP 719 723 beta beta NN 724 726 is be VBZ 727 739 considerably considerably RB 740 744 more more RBR 745 751 stable stable JJ 752 756 than than IN 757 758 I i NN 759 764 kappa kappa NN 765 766 B B NNP 767 772 alpha alpha NN 772 773 . . . 774 777 The the DT 778 787 half-life half-life NN 788 790 of of IN 791 795 both both DT 796 806 inhibitors inhibitor NNS 807 809 is be VBZ 810 819 increased increase VBN 820 822 in in IN 823 827 HeLa HeLa NNP 828 833 cells cell NNS 833 834 . . . 835 837 In in IN 838 846 contrast contrast NN 846 847 , , , 848 851 all all DT 852 857 other other JJ 858 866 NF-kappa NF-kappa NNP 867 870 B/I B/I NNP 871 876 kappa kappa NN 877 878 B B NNP 879 888 molecules molecule NNS 889 895 tested test VBN 896 899 are be VBP 900 910 relatively relatively RB 911 917 stable stable JJ 918 920 in in IN 921 925 both both DT 926 936 cell-types cell-type NNS 936 937 . . . 938 941 The the DT 942 950 elevated elevated JJ 951 959 turnover turnover NN 960 962 of of IN 963 973 endogenous endogenous JJ 974 975 I i NN 976 981 kappa kappa NN 982 983 B B NNP 984 989 alpha alpha NN 990 992 in in IN 993 1000 Namalwa Namalwa NNP 1001 1006 cells cell NNS 1007 1009 is be VBZ 1010 1019 inhibited inhibit VBN 1020 1022 by by IN 1023 1024 a a DT 1025 1035 proteasome proteasome NN 1036 1045 inhibitor inhibitor NN 1046 1049 and and CC 1050 1054 thus thus RB 1055 1060 seems seem VBZ 1061 1063 to to TO 1064 1066 be be VB 1067 1073 driven drive VBN 1074 1076 by by IN 1077 1080 the the DT 1081 1085 same same JJ 1086 1097 degradation degradation NN 1098 1107 machinery machinery NN 1108 1110 as as IN 1111 1114 the the DT 1115 1121 slower slow JJR 1122 1130 turnover turnover NN 1131 1133 in in IN 1134 1139 non-B non-b JJ 1140 1145 cells cell NNS 1145 1146 . . . 1147 1158 Furthermore furthermore RB 1158 1159 , , , 1160 1162 we we PRP 1163 1175 investigated investigate VBD 1176 1179 the the DT 1180 1189 processes process NNS 1190 1198 involved involve VBN 1199 1201 in in IN 1202 1212 persistent persistent JJ 1213 1223 activation activation NN 1224 1226 of of IN 1227 1235 NF-kappa NF-kappa NNP 1236 1238 B. B. NNP 1239 1248 TNF-alpha TNF-alpha NNP 1249 1258 signaling signaling NN 1259 1264 leads lead VBZ 1265 1267 to to TO 1268 1269 a a DT 1270 1275 rapid rapid JJ 1276 1285 depletion depletion NN 1286 1288 of of IN 1289 1297 cellular cellular JJ 1298 1299 I i NN 1300 1305 kappa kappa NN 1306 1307 B B NNP 1308 1312 beta beta NN 1313 1318 pools pool NNS 1318 1319 . . . 1320 1321 I i NN 1322 1327 kappa kappa NN 1328 1329 B B NNP 1330 1335 alpha alpha NN 1336 1338 is be VBZ 1339 1350 efficiently efficiently RB 1351 1364 resynthesized resynthesize VBN 1365 1372 whereas whereas IN 1373 1374 I i NN 1375 1380 kappa kappa NN 1381 1382 B B NNP 1383 1387 beta beta NN 1388 1394 levels level NNS 1395 1399 stay stay VBP 1400 1403 low low JJ 1404 1407 for for IN 1408 1409 a a DT 1410 1419 prolonged prolong VBN 1420 1424 time time NN 1424 1425 . . . 1426 1434 NF-kappa NF-kappa NNP 1435 1436 B B NNP 1437 1444 binding binding NN 1445 1453 activity activity NN 1454 1457 can can MD 1458 1460 be be VB 1461 1469 detected detect VBN 1470 1473 for for IN 1474 1481 several several JJ 1482 1487 hours hour NNS 1488 1493 after after IN 1494 1505 stimulation stimulation NN 1505 1506 . . . 1507 1509 We we PRP 1510 1515 found find VBD 1516 1520 that that IN 1521 1528 removal removal NN 1529 1531 of of IN 1532 1535 the the DT 1536 1545 TNF-alpha TNF-alpha NNP 1546 1556 containing contain VBG 1557 1563 medium medium NN 1564 1570 causes cause VBZ 1571 1572 a a DT 1573 1578 rapid rapid JJ 1579 1587 decrease decrease NN 1588 1590 in in IN 1591 1598 nuclear nuclear JJ 1599 1607 NF-kappa NF-kappa NNP 1608 1610 B. B. NNP 1611 1612 A a NN 1613 1624 phosphoform phosphoform NN 1625 1627 of of IN 1628 1633 newly newly RB 1634 1645 synthesized synthesize VBN 1646 1647 I i NN 1648 1653 kappa kappa NN 1654 1655 B B NNP 1656 1661 alpha alpha NN 1662 1664 is be VBZ 1665 1672 visible visible JJ 1673 1677 when when WRB 1678 1689 degradation degradation NN 1690 1692 by by IN 1693 1696 the the DT 1697 1707 proteasome proteasome NN 1708 1710 is be VBZ 1711 1720 inhibited inhibit VBN 1721 1724 and and CC 1725 1728 new new JJ 1729 1730 I i NN 1731 1736 kappa kappa NN 1737 1738 B B NNP 1739 1744 alpha alpha NN 1745 1753 displays display VBZ 1754 1757 the the DT 1758 1762 same same JJ 1763 1773 properties property NNS 1774 1783 regarding regard VBG 1784 1799 phosphorylation phosphorylation NN 1800 1803 and and CC 1804 1815 degradation degradation NN 1816 1818 in in IN 1819 1827 response response NN 1828 1830 to to TO 1831 1832 a a DT 1833 1839 second second JJ 1840 1847 inducer inducer NN 1847 1848 . . . 1849 1854 There there EX 1855 1857 is be VBZ 1858 1860 no no DT 1861 1872 significant significant JJ 1873 1883 difference difference NN 1884 1886 in in IN 1887 1890 the the DT 1891 1899 turnover turnover NN 1900 1902 of of IN 1903 1907 pre- pre- JJ 1908 1911 and and CC 1912 1926 post-inductive post-inductive JJ 1927 1928 I i NN 1929 1934 kappa kappa NN 1935 1936 B B NNP 1937 1942 alpha alpha NN 1942 1943 . . . 1944 1949 These these DT 1950 1962 observations observation NNS 1963 1970 suggest suggest VBP 1971 1975 that that IN 1976 1987 resynthesis resynthesis NN 1988 1990 of of IN 1991 1992 I i NN 1993 1998 kappa kappa NN 1999 2000 B B NNP 2001 2006 alpha alpha NN 2007 2010 and and CC 2011 2018 removal removal NN 2019 2021 of of IN 2022 2025 the the DT 2026 2034 stimulus stimulus NN 2035 2038 are be VBP 2039 2049 obligatory obligatory JJ 2050 2055 steps step NNS 2056 2059 for for IN 2060 2063 the the DT 2064 2076 inactivation inactivation NN 2077 2079 of of IN 2080 2087 nuclear nuclear JJ 2088 2090 NF NF NNP 2091 2096 kappa kappa NN 2097 2098 B B NNP 2098 2099 . . .