0 16 3-deazaadenosine 3-deazaadenosine NN 16 17 , , , 18 19 a a DT 20 42 S-adenosylhomocysteine S-adenosylhomocysteine NNP 43 52 hydrolase hydrolase NN 53 62 inhibitor inhibitor NN 62 63 , , , 64 67 has have VBZ 68 72 dual dual JJ 73 80 effects effect NNS 81 83 on on IN 84 93 NF-kappaB NF-kappaB NNP 94 104 regulation regulation NN 104 105 . . . 106 116 Inhibition Inhibition NNP 117 119 of of IN 120 129 NF-kappaB NF-kappaB NNP 130 145 transcriptional transcriptional JJ 146 154 activity activity NN 155 158 and and CC 159 168 promotion promotion NN 169 171 of of IN 172 184 IkappaBalpha IkappaBalpha NNP 185 196 degradation degradation NN 196 197 . . . 199 209 Previously previously RB 210 212 we we PRP 213 221 reported report VBD 222 226 that that IN 227 243 3-deazaadenosine 3-deazaadenosine NN 244 245 ( ( ( 245 248 DZA DZA NNP 248 249 ) ) ) 249 250 , , , 251 252 a a DT 253 259 potent potent JJ 260 269 inhibitor inhibitor NN 270 273 and and CC 274 283 substrate substrate NN 284 287 for for IN 288 310 S-adenosylhomocysteine S-adenosylhomocysteine NNP 311 320 hydrolase hydrolase NN 321 329 inhibits inhibit VBZ 330 339 bacterial bacterial JJ 340 366 lipopolysaccharide-induced lipopolysaccharide-induced JJ 367 380 transcription transcription NN 381 383 of of IN 384 389 tumor tumor NN 390 398 necrosis necrosis NN 399 411 factor-alpha factor-alpha NN 412 415 and and CC 416 433 interleukin-1beta interleukin-1beta NN 434 436 in in IN 437 442 mouse mouse NN 443 453 macrophage macrophage NN 454 457 RAW RAW NNP 458 463 264.7 264.7 CD 464 469 cells cell NNS 469 470 . . . 471 473 In in IN 474 478 this this DT 479 484 study study NN 484 485 , , , 486 488 we we PRP 489 500 demonstrate demonstrate VBP 501 504 the the DT 505 512 effects effect NNS 513 515 of of IN 516 519 DZA DZA NNP 520 522 on on IN 523 530 nuclear nuclear JJ 531 544 factor-kappaB factor-kappaB NNP 545 546 ( ( ( 546 555 NF-kappaB NF-kappaB NNP 555 556 ) ) ) 557 567 regulation regulation NN 567 568 . . . 569 572 DZA DZA NNP 573 581 inhibits inhibit VBZ 582 585 the the DT 586 601 transcriptional transcriptional JJ 602 610 activity activity NN 611 613 of of IN 614 623 NF-kappaB NF-kappaB NNP 624 631 through through IN 632 635 the the DT 636 645 hindrance hindrance NN 646 648 of of IN 649 652 p65 p65 NN 653 654 ( ( ( 654 659 Rel-A Rel-A NNP 659 660 ) ) ) 661 676 phosphorylation phosphorylation NN 677 684 without without IN 685 694 reduction reduction NN 695 697 of of IN 698 701 its its PRP$ 702 709 nuclear nuclear JJ 710 723 translocation translocation NN 724 727 and and CC 728 731 DNA dna NN 732 739 binding binding NN 740 748 activity activity NN 748 749 . . . 750 753 The the DT 754 764 inhibitory inhibitory JJ 765 771 effect effect NN 772 774 of of IN 775 778 DZA DZA NNP 779 781 on on IN 782 791 NF-kappaB NF-kappaB NNP 792 807 transcriptional transcriptional JJ 808 816 activity activity NN 817 819 is be VBZ 820 831 potentiated potentiate VBN 832 834 by by IN 835 838 the the DT 839 847 addition addition NN 848 850 of of IN 851 863 homocysteine homocysteine NN 863 864 . . . 865 870 Taken take VBN 871 879 together together RB 879 880 , , , 881 884 DZA DZA NNP 885 893 promotes promote VBZ 894 897 the the DT 898 909 proteolytic proteolytic JJ 910 921 degradation degradation NN 922 924 of of IN 925 937 IkappaBalpha IkappaBalpha NNP 937 938 , , , 939 942 but but CC 943 946 not not RB 947 958 IkappaBbeta IkappaBbeta NNP 958 959 , , , 960 969 resulting result VBG 970 972 in in IN 973 975 an an DT 976 984 increase increase NN 985 987 of of IN 988 991 DNA DNA NNP 992 999 binding binding NN 1000 1008 activity activity NN 1009 1011 of of IN 1012 1021 NF-kappaB NF-kappaB NNP 1022 1024 in in IN 1025 1028 the the DT 1029 1036 nucleus nucleus NN 1037 1039 in in IN 1040 1043 the the DT 1044 1051 absence absence NN 1052 1054 of of IN 1055 1058 its its PRP$ 1059 1074 transcriptional transcriptional JJ 1075 1083 activity activity NN 1084 1086 in in IN 1087 1090 RAW RAW NNP 1091 1096 264.7 264.7 CD 1097 1102 cells cell NNS 1102 1103 . . . 1104 1107 The the DT 1108 1117 reduction reduction NN 1118 1120 of of IN 1121 1133 IkappaBalpha IkappaBalpha NNP 1134 1136 by by IN 1137 1140 DZA DZA NNP 1141 1143 is be VBZ 1144 1151 neither neither CC 1152 1160 involved involve VBN 1161 1163 in in IN 1164 1171 IkappaB IkappaB NNP 1172 1178 kinase kinase NNP 1179 1186 complex complex NN 1187 1197 activation activation NN 1198 1201 nor nor CC 1202 1211 modulated modulate VBN 1212 1214 by by IN 1215 1218 the the DT 1219 1227 addition addition NN 1228 1230 of of IN 1231 1243 homocysteine homocysteine NN 1243 1244 . . . 1245 1249 This this DT 1250 1255 study study NN 1256 1264 strongly strongly RB 1265 1273 suggests suggest VBZ 1274 1278 that that IN 1279 1282 DZA DZA NNP 1283 1286 may may MD 1287 1289 be be VB 1290 1291 a a DT 1292 1298 potent potent JJ 1299 1303 drug drug NN 1304 1307 for for IN 1308 1311 the the DT 1312 1321 treatment treatment NN 1322 1324 of of IN 1325 1333 diseases disease NNS 1334 1336 in in IN 1337 1342 which which WDT 1343 1352 NF-kappaB NF-kappaB NNP 1353 1358 plays play VBZ 1359 1360 a a DT 1361 1368 central central JJ 1369 1379 pathogenic pathogenic JJ 1380 1384 role role NN 1384 1385 , , , 1386 1388 as as RB 1389 1393 well well RB 1394 1396 as as IN 1397 1398 a a DT 1399 1405 useful useful JJ 1406 1410 tool tool NN 1411 1414 for for IN 1415 1423 studying study VBG 1424 1427 the the DT 1428 1438 regulation regulation NN 1439 1442 and and CC 1443 1456 physiological physiological JJ 1457 1466 functions function NNS 1467 1469 of of IN 1470 1479 NF-kappaB NF-kappaB NNP 1479 1480 . . .