0 8 Cleavage Cleavage NNP 9 11 of of IN 12 25 transcription transcription NN 26 32 factor factor NN 33 36 SP1 sp1 NN 37 39 by by IN 40 48 caspases caspas NNS 49 55 during during IN 56 72 anti-IgM-induced anti-igm-induced JJ 73 79 B-cell b-cell NN 80 89 apoptosis apoptosis NN 89 90 . . . 92 101 Apoptosis Apoptosis NNP 102 104 is be VBZ 105 117 instrumental instrumental JJ 118 120 in in IN 121 124 the the DT 125 134 processes process NNS 135 145 generating generate VBG 146 149 the the DT 150 159 diversity diversity NN 160 162 of of IN 163 166 the the DT 167 173 B-cell b-cell NN 174 184 repertoire repertoire NN 184 185 . . . 186 198 Autoreactive autoreactive JJ 199 206 B-cells B-cell NNPS 207 210 are be VBP 211 221 eliminated eliminate VBN 222 224 by by IN 225 233 anti-IgM anti-igm JJ 234 246 crosslinking crosslinking NN 247 252 after after IN 253 265 encountering encounter VBG 266 279 self-antigens self-antigen NNS 279 280 , , , 281 284 but but CC 285 292 precise precise JJ 293 303 mechanisms mechanism NNS 304 311 leading lead VBG 312 314 to to TO 315 321 B-cell b-cell NN 322 331 apoptosis apoptosis NN 332 335 are be VBP 336 341 still still RB 342 345 not not RB 346 350 well well RB 351 361 understood understand VBN 361 362 . . . 363 365 We we PRP 366 372 report report VBP 373 377 here here RB 378 381 the the DT 382 390 cleavage cleavage NN 391 393 of of IN 394 397 the the DT 398 411 transcription transcription NN 412 418 factor factor NN 419 422 SP1 sp1 NN 423 425 in in IN 426 429 the the DT 430 435 human human JJ 436 443 Burkitt Burkitt NNP 444 452 lymphoma lymphoma NN 453 457 cell cell NN 458 462 line line NN 463 467 BL60 bl60 NN 468 474 during during IN 475 491 anti-IgM-induced anti-igm-induced JJ 492 501 apoptosis apoptosis NN 501 502 . . . 503 510 Western western NN 511 515 blot blot NN 516 524 analysis analysis NN 525 533 revealed reveal VBD 534 537 two two CD 538 546 cleavage cleavage NN 547 555 products product NNS 556 558 of of IN 559 572 approximately approximately RB 573 575 68 68 CD 576 579 kDa kda NN 580 583 and and CC 584 586 45 45 CD 587 590 kDa kda NN 591 596 after after IN 597 606 induction induction NN 607 609 of of IN 610 619 apoptosis apoptosis NN 619 620 . . . 621 629 Cleavage Cleavage NNP 630 635 could could MD 636 638 be be VB 639 649 completely completely RB 650 659 inhibited inhibit VBN 660 662 by by IN 663 672 zDEVD-fmk zdevd-fmk NN 672 673 , , , 674 676 an an DT 677 686 inhibitor inhibitor NN 687 695 specific specific JJ 696 699 for for IN 700 707 caspase caspase NN 708 714 3-like 3-like JJ 715 724 proteases protease NNS 724 725 . . . 726 734 In-vitro in-vitro FW 735 743 cleavage cleavage NN 744 746 of of IN 747 758 recombinant recombinant JJ 759 762 SP1 sp1 NN 763 765 by by IN 766 777 recombinant recombinant JJ 778 785 caspase caspase NN 786 787 3 3 CD 788 789 ( ( ( 789 794 CPP32 CPP32 NNP 794 795 ) ) ) 796 798 or or CC 799 806 caspase caspase NN 807 808 7 7 CD 809 810 ( ( ( 810 813 Mch Mch NNP 814 815 3 3 CD 815 816 ) ) ) 817 824 results result VBZ 825 827 in in IN 828 835 similar similar JJ 836 844 cleavage cleavage NN 845 853 products product NNS 854 856 as as IN 857 862 those those DT 863 871 observed observe VBN 872 874 in in FW 875 879 vivo vivo FW 879 880 . . . 881 892 Recombinant recombinant JJ 893 900 caspase caspase NN 901 902 6 6 CD 903 904 ( ( ( 904 907 Mch Mch NNP 908 909 2 2 CD 909 910 ) ) ) 911 920 primarily primarily RB 921 930 generates generate VBZ 931 932 a a DT 933 939 68-kDa 68-kda JJ 940 948 cleavage cleavage NN 949 956 product product NN 956 957 , , , 958 960 as as IN 961 969 observed observe VBN 970 975 after after IN 976 983 calcium calcium NN 984 993 ionophore ionophore NN 994 995 ( ( ( 995 998 CaI CaI NNP 998 999 ) ) ) 1000 1007 induced induce VBD 1008 1014 B-cell b-cell NN 1015 1025 apoptosis. apoptosis. NN 1026 1028 In in IN 1029 1037 contrast contrast NN 1037 1038 , , , 1039 1046 caspase caspase NN 1047 1048 1 1 CD 1049 1050 ( ( ( 1050 1053 ICE ICE NNP 1053 1054 ) ) ) 1055 1058 did do VBD 1059 1062 not not RB 1063 1069 cleave cleave VB 1070 1073 SP1 sp1 NN 1074 1076 in in FW 1077 1082 vitro vitro FW 1082 1083 . . . 1084 1087 The the DT 1088 1092 time time NN 1093 1099 course course NN 1100 1102 of of IN 1103 1106 SP1 sp1 NN 1107 1115 cleavage cleavage NN 1116 1122 during during IN 1123 1139 anti-IgM-induced anti-igm-induced JJ 1140 1149 apoptosis apoptosis NN 1150 1152 is be VBZ 1153 1163 paralleled parallel VBN 1164 1166 by by IN 1167 1169 an an DT 1170 1178 increase increase NN 1179 1181 of of IN 1182 1189 caspase caspase NN 1190 1198 activity activity NN 1199 1207 measured measure VBN 1208 1210 by by IN 1211 1230 DEVD-p-nitroanilide DEVD-p-nitroanilide NNP 1231 1232 ( ( ( 1232 1240 DEVD-pNA DEVD-pNA NNP 1240 1241 ) ) ) 1242 1250 cleavage cleavage NN 1250 1251 . . . 1252 1255 DNA DNA NNP 1256 1266 band-shift band-shift NN 1267 1273 assays assay NNS 1274 1282 revealed reveal VBD 1283 1284 a a DT 1285 1293 decrease decrease NN 1294 1296 in in IN 1297 1300 the the DT 1301 1310 intensity intensity NN 1311 1313 of of IN 1314 1317 the the DT 1318 1322 full full JJ 1323 1329 length length NN 1330 1337 SP1/DNA sp1/dna NN 1338 1345 complex complex NN 1346 1349 and and CC 1350 1352 an an DT 1353 1361 increase increase NN 1362 1364 in in IN 1365 1368 the the DT 1369 1378 intensity intensity NN 1379 1381 of of IN 1382 1383 a a DT 1384 1391 smaller small JJR 1392 1399 complex complex NN 1400 1403 due due JJ 1404 1406 to to TO 1407 1410 the the DT 1411 1418 binding binding NN 1419 1421 of of IN 1422 1425 one one CD 1426 1429 SP1 sp1 NN 1430 1438 cleavage cleavage NN 1439 1446 product product NN 1446 1447 . . . 1448 1450 By by IN 1451 1456 Edman Edman NNP 1457 1467 sequencing sequencing NN 1468 1470 we we PRP 1471 1476 could could MD 1477 1485 identify identify VB 1486 1487 a a DT 1488 1495 caspase caspase NN 1496 1497 3 3 CD 1498 1506 cleavage cleavage NN 1507 1511 site site NN 1512 1517 after after IN 1518 1524 Asp584 Asp584 NNP 1525 1526 ( ( ( 1526 1537 D584AQPQAGR D584AQPQAGR NNP 1537 1538 ) ) ) 1538 1539 , , , 1540 1550 generating generate VBG 1551 1552 a a DT 1553 1559 22-kDa 22-kda JJ 1560 1570 C-terminal c-terminal JJ 1571 1574 SP1 sp1 NN 1575 1582 protein protein NN 1583 1591 fragment fragment NN 1592 1597 which which WDT 1598 1603 still still RB 1604 1612 contains contain VBZ 1613 1616 the the DT 1617 1620 DNA dna NN 1621 1628 binding binding NN 1629 1633 site site NN 1633 1634 . . . 1635 1638 Our our PRP$ 1639 1646 results result NNS 1647 1651 show show VBP 1652 1655 the the DT 1656 1664 cleavage cleavage NN 1665 1667 of of IN 1668 1671 the the DT 1672 1677 human human JJ 1678 1691 transcription transcription NN 1692 1698 factor factor NN 1699 1702 SP1 sp1 NN 1703 1705 in in FW 1706 1710 vivo vivo FW 1711 1714 and and CC 1715 1717 in in FW 1718 1723 vitro vitro FW 1723 1724 , , , 1725 1736 underlining underline VBG 1737 1740 the the DT 1741 1748 central central JJ 1749 1753 role role NN 1754 1756 of of IN 1757 1764 caspase caspase NN 1765 1771 3-like 3-like JJ 1772 1781 proteases protease NNS 1782 1788 during during IN 1789 1792 the the DT 1793 1800 process process NN 1801 1803 of of IN 1804 1820 anti-IgM-induced anti-igm-induced JJ 1821 1830 apoptosis apoptosis NN 1830 1831 . . .