0 13 Transcription transcription NN 14 21 factors factor NNS 22 24 as as IN 25 32 targets target NNS 33 36 for for IN 37 46 oxidative oxidative JJ 47 57 signalling signalling NN 58 64 during during IN 65 75 lymphocyte lymphocyte NN 76 86 activation activation NN 86 87 . . . 89 91 We we PRP 92 102 previously previously RB 103 107 have have VBP 108 120 demonstrated demonstrate VBN 121 122 a a DT 123 134 requirement requirement NN 135 138 for for IN 139 148 oxidative oxidative JJ 149 155 events event NNS 156 162 during during IN 163 167 cell cell NN 168 173 cycle cycle NN 174 179 entry entry NN 180 182 in in IN 183 184 T t NN 185 196 lymphocytes lymphocyte NNS 197 200 and and CC 201 205 have have VBP 206 218 hypothesised hypothesise VBN 219 223 that that IN 224 232 reactive reactive JJ 233 239 oxygen oxygen NN 240 247 species specie NNS 248 251 may may MD 252 255 act act VB 256 258 as as IN 259 272 intracellular intracellular JJ 273 283 signalling signalling NN 284 290 agents agent NNS 291 297 during during IN 298 308 lymphocyte lymphocyte NN 309 319 activation activation NN 319 320 . . . 321 323 In in IN 324 327 the the DT 328 335 current current JJ 336 341 study study NN 341 342 , , , 343 353 cysteamine cysteamine NN 353 354 , , , 355 357 an an DT 358 368 aminothiol aminothiol NN 369 377 compound compound NN 378 382 with with IN 383 394 antioxidant antioxidant JJ 395 403 activity activity NN 403 404 , , , 405 408 has have VBZ 409 413 been be VBN 414 418 used use VBN 419 421 to to TO 422 429 further further RB 430 441 investigate investigate VB 442 445 the the DT 446 450 role role NN 451 453 of of IN 454 463 oxidative oxidative JJ 464 474 signalling signalling NN 475 481 during during IN 482 492 lymphocyte lymphocyte NN 493 503 activation activation NN 503 504 . . . 505 514 Treatment Treatment NNP 515 517 of of IN 518 524 normal normal JJ 525 530 human human JJ 531 541 peripheral peripheral JJ 542 547 blood blood NN 548 559 lymphocytes lymphocyte NNS 560 564 with with IN 565 575 cysteamine cysteamine NN 576 578 in in FW 579 584 vitro vitro FW 585 588 was be VBD 589 594 found find VBN 595 597 to to TO 598 605 inhibit inhibit VB 606 619 proliferation proliferation NN 620 622 in in IN 623 624 a a DT 625 639 dose-dependent dose-dependent JJ 640 646 manner manner NN 646 647 , , , 648 652 with with IN 653 664 essentially essentially RB 665 673 complete complete JJ 674 684 inhibition inhibition NN 685 694 occurring occur VBG 695 697 at at IN 698 699 a a DT 700 704 dose dose NN 705 707 of of IN 708 711 400 400 CD 712 718 microM microm NN 718 719 . . . 720 724 This this DT 725 735 inhibitory inhibitory JJ 736 742 effect effect NN 743 746 was be VBD 747 754 limited limit VBN 755 757 to to TO 758 761 the the DT 762 767 first first JJ 768 769 2 2 CD 770 771 h h NN 772 777 after after IN 778 787 mitogenic mitogenic JJ 788 798 activation activation NN 798 799 , , , 800 810 localizing localize VBG 811 814 the the DT 815 825 time-frame time-frame NN 826 828 of of IN 829 835 action action NN 836 838 of of IN 839 849 cysteamine cysteamine NN 850 852 to to TO 853 859 within within IN 860 863 the the DT 864 874 commitment commitment NN 875 881 period period NN 881 882 . . . 883 885 It it PRP 886 895 therefore therefore RB 896 899 was be VBD 900 902 of of IN 903 911 interest interest NN 912 914 to to TO 915 924 establish establish VB 925 930 which which WDT 930 931 , , , 932 934 if if IN 935 938 any any DT 938 939 , , , 940 950 commitment commitment NN 951 957 events event NNS 958 962 were be VBD 963 971 affected affect VBN 972 974 by by IN 975 984 oxidative oxidative JJ 985 995 signalling signalling NN 996 1002 during during IN 1003 1007 cell cell NN 1008 1013 cycle cycle NN 1014 1019 entry entry NN 1019 1020 . . . 1021 1027 Taking take VBG 1028 1031 the the DT 1032 1036 IL-2 il-2 NN 1037 1041 gene gene NN 1042 1044 as as IN 1045 1046 a a DT 1047 1056 candidate candidate NN 1056 1057 , , , 1058 1060 we we PRP 1061 1069 examined examine VBD 1070 1073 the the DT 1074 1080 effect effect NN 1081 1083 of of IN 1084 1094 cysteamine cysteamine NN 1095 1104 treatment treatment NN 1105 1107 on on IN 1108 1113 early early JJ 1114 1118 gene gene NN 1119 1129 expression expression NN 1130 1136 during during IN 1137 1147 lymphocyte lymphocyte NN 1148 1158 activation activation NN 1158 1159 , , , 1160 1163 and and CC 1164 1166 on on IN 1167 1170 the the DT 1171 1179 activity activity NN 1180 1182 of of IN 1183 1196 transcription transcription NN 1197 1204 factors factor NNS 1205 1209 AP-1 ap-1 NN 1209 1210 , , , 1211 1219 NF-kappa NF-kappa NNP 1220 1221 B B NNP 1221 1222 , , , 1223 1228 NF-AT NF-AT NNP 1229 1232 and and CC 1233 1237 Oct1 Oct1 NNP 1237 1238 , , , 1239 1244 whose whose WP$ 1245 1254 functions function NNS 1255 1258 are be VBP 1259 1267 required require VBN 1268 1271 for for IN 1272 1282 expression expression NN 1283 1285 of of IN 1286 1289 the the DT 1290 1294 IL-2 il-2 NN 1295 1299 mRNA mrna NN 1299 1300 . . . 1301 1311 Cysteamine Cysteamine NNP 1312 1321 treatment treatment NN 1322 1331 inhibited inhibit VBD 1332 1336 both both CC 1337 1347 expression expression NN 1348 1350 of of IN 1351 1354 the the DT 1355 1359 IL-2 il-2 NN 1360 1364 mRNA mrna NN 1365 1368 and and CC 1369 1378 secretion secretion NN 1379 1381 of of IN 1382 1386 IL-2 il-2 NN 1387 1391 into into IN 1392 1395 the the DT 1396 1403 culture culture NN 1404 1410 medium medium NN 1410 1411 . . . 1412 1415 The the DT 1416 1426 inhibitory inhibitory JJ 1427 1433 effect effect NN 1434 1436 of of IN 1437 1447 cysteamine cysteamine NN 1448 1451 may may MD 1452 1454 be be VB 1455 1463 mediated mediate VBN 1464 1466 at at IN 1467 1472 least least JJS 1473 1475 in in IN 1476 1480 part part NN 1481 1483 by by IN 1484 1486 an an DT 1487 1493 effect effect NN 1494 1496 on on IN 1497 1510 transcription transcription NN 1511 1517 factor factor NN 1518 1526 function function NN 1526 1527 , , , 1528 1530 as as IN 1531 1534 the the DT 1535 1538 DNA dna NN 1539 1546 binding binding NN 1547 1557 activities activity NNS 1558 1560 of of IN 1561 1565 AP-1 AP-1 NNP 1566 1569 and and CC 1570 1578 NF-kappa NF-kappa NNP 1579 1580 B B NNP 1581 1590 extracted extract VBN 1591 1595 from from IN 1596 1614 mitogen-stimulated mitogen-stimulated JJ 1615 1620 cells cell NNS 1621 1625 were be VBD 1626 1639 significantly significantly RB 1640 1649 inhibited inhibit VBN 1650 1652 by by IN 1653 1663 cysteamine cysteamine NN 1664 1673 treatment treatment NN 1673 1674 . . . 1675 1688 Interestingly interestingly RB 1688 1689 , , , 1690 1694 Oct1 Oct1 NNP 1695 1698 and and CC 1699 1704 NF-AT NF-AT NNP 1705 1708 DNA DNA NNP 1709 1716 binding binding NN 1717 1725 activity activity NN 1726 1730 were be VBD 1731 1734 not not RB 1735 1743 affected affect VBN 1744 1746 by by IN 1747 1757 cysteamine cysteamine NN 1758 1767 treatment treatment NN 1767 1768 , , , 1769 1779 suggesting suggest VBG 1780 1784 that that IN 1785 1794 oxidative oxidative JJ 1795 1805 signalling signalling NN 1806 1815 processes process NNS 1816 1823 operate operate VBP 1824 1826 in in IN 1827 1828 a a DT 1829 1838 selective selective JJ 1839 1845 manner manner NN 1845 1846 . . . 1847 1850 The the DT 1851 1865 identification identification NN 1866 1868 of of IN 1869 1879 regulatory regulatory JJ 1880 1888 proteins protein NNS 1888 1889 , , , 1890 1894 such such JJ 1895 1897 as as IN 1898 1911 transcription transcription NN 1912 1919 factors factor NNS 1919 1920 , , , 1921 1923 as as IN 1924 1933 molecular molecular JJ 1934 1941 targets target NNS 1942 1945 for for IN 1946 1955 oxidative oxidative JJ 1956 1966 signalling signalling NN 1967 1975 provides provide VBZ 1976 1983 further further JJ 1984 1992 evidence evidence NN 1993 1995 to to TO 1996 2005 implicate implicate VB 2006 2015 oxidative oxidative JJ 2016 2026 signalling signalling NN 2027 2029 as as IN 2030 2035 being be VBG 2036 2046 intimately intimately RB 2047 2055 involved involve VBN 2056 2058 in in IN 2059 2062 the the DT 2063 2065 G0 g0 NN 2066 2068 to to TO 2069 2071 G1 g1 NN 2072 2077 phase phase NN 2078 2088 transition transition NN 2089 2091 in in IN 2092 2093 T t NN 2094 2105 lymphocytes lymphocyte NNS 2105 2106 . . .