0 7 Control Control NNP 8 10 of of IN 11 17 NFATx1 nfatx1 NN 18 25 nuclear nuclear JJ 26 39 translocation translocation NN 40 42 by by IN 43 44 a a DT 45 66 calcineurin-regulated calcineurin-regulated JJ 67 77 inhibitory inhibitory JJ 78 84 domain domain NN 84 85 . . . 87 90 The the DT 91 98 nuclear nuclear JJ 99 105 factor factor NN 106 108 of of IN 109 118 activated activate VBN 119 120 T t NN 121 126 cells cell NNS 127 128 ( ( ( 128 132 NFAT NFAT NNP 132 133 ) ) ) 134 143 regulates regulate VBZ 144 152 cytokine cytokine NN 153 157 gene gene NN 158 168 expression expression NN 169 171 in in IN 172 173 T t NN 174 179 cells cell NNS 180 187 through through IN 188 198 cis-acting cis-acting JJ 199 207 elements element NNS 208 215 located located JJ 216 218 in in IN 219 222 the the DT 223 232 promoters promoter NNS 233 235 of of IN 236 243 several several JJ 244 252 cytokine cytokine NN 253 258 genes gene NNS 258 259 . . . 260 266 NFATx1 NFATx1 NNP 266 267 , , , 268 273 which which WDT 274 276 is be VBZ 277 291 preferentially preferentially RB 292 301 expressed express VBN 302 304 in in IN 305 308 the the DT 309 315 thymus thymus NN 316 319 and and CC 320 330 peripheral peripheral JJ 331 336 blood blood NN 337 347 leukocytes leukocyte NNS 347 348 , , , 349 351 is be VBZ 352 355 one one CD 356 358 of of IN 359 363 four four CD 364 371 members member NNS 372 374 of of IN 375 378 the the DT 379 383 NFAT nfat NN 384 390 family family NN 391 393 of of IN 394 407 transcription transcription NN 408 415 factors factor NNS 415 416 . . . 417 419 We we PRP 420 424 have have VBP 425 434 performed perform VBN 435 441 domain domain NN 442 450 analysis analysis NN 451 453 of of IN 454 460 NFATx1 nfatx1 NN 461 463 by by IN 464 473 examining examine VBG 474 477 the the DT 478 485 effects effect NNS 486 488 of of IN 489 497 deletion deletion NN 498 507 mutations mutation NNS 507 508 . . . 509 511 We we PRP 512 517 found find VBD 518 522 that that IN 523 529 NFATx1 nfatx1 NN 530 533 DNA DNA NNP 534 541 binding binding NN 542 550 activity activity NN 551 554 and and CC 555 566 interaction interaction NN 567 571 with with IN 572 576 AP-1 ap-1 NN 577 589 polypeptides polypeptide NNS 590 594 were be VBD 595 604 dependent dependent JJ 605 607 on on IN 608 611 its its PRP$ 612 619 central central JJ 620 623 Rel Rel NNP 624 634 similarity similarity NN 635 641 region region NN 642 645 and and CC 646 650 that that IN 651 666 transcriptional transcriptional JJ 667 677 activation activation NN 678 681 was be VBD 682 689 reduced reduce VBN 690 692 by by IN 693 702 deletions deletion NNS 703 705 of of IN 706 712 either either CC 713 716 its its PRP$ 717 727 N-terminal n-terminal JJ 728 734 domain domain NN 735 737 or or CC 738 741 its its PRP$ 742 752 C-terminal c-terminal JJ 753 759 domain domain NN 759 760 , , , 761 771 suggesting suggest VBG 772 775 the the DT 776 784 presence presence NN 785 787 of of IN 788 797 intrinsic intrinsic JJ 798 813 transcriptional transcriptional JJ 814 824 activation activation NN 825 831 motifs motif NNS 832 834 in in IN 835 839 both both DT 840 847 regions region NNS 847 848 . . . 849 851 We we PRP 852 856 also also RB 857 867 identified identify VBD 868 869 a a DT 870 876 potent potent JJ 877 887 inhibitory inhibitory JJ 888 896 sequence sequence NN 897 903 within within IN 904 907 its its PRP$ 908 918 N-terminal n-terminal JJ 919 925 domain domain NN 925 926 . . . 927 929 We we PRP 930 934 show show VBP 935 939 that that IN 940 943 the the DT 944 956 inactivation inactivation NN 957 959 of of IN 960 963 the the DT 964 974 inhibition inhibition NN 975 978 was be VBD 979 988 dependent dependent JJ 989 991 on on IN 992 995 the the DT 996 1004 activity activity NN 1005 1007 of of IN 1008 1019 calcineurin calcineurin NN 1019 1020 , , , 1021 1022 a a DT 1023 1051 calcium-calmodulin-dependent calcium-calmodulin-dependent JJ 1052 1063 phosphatase phosphatase NN 1063 1064 . . . 1065 1067 We we PRP 1068 1072 also also RB 1073 1077 show show VBP 1078 1082 that that IN 1083 1094 calcineurin calcineurin NN 1095 1105 associated associate VBN 1106 1110 with with IN 1111 1114 the the DT 1115 1125 N-terminal n-terminal JJ 1126 1132 domain domain NN 1133 1135 of of IN 1136 1142 NFATx1 nfatx1 NN 1143 1145 at at IN 1146 1154 multiple multiple JJ 1155 1162 docking docking NN 1163 1168 sites site NNS 1169 1172 and and CC 1173 1179 caused cause VBD 1180 1181 a a DT 1182 1191 reduction reduction NN 1192 1194 of of IN 1195 1199 size size NN 1199 1200 , , , 1201 1211 indicative indicative JJ 1212 1214 of of IN 1215 1232 dephosphorylation dephosphorylation NN 1232 1233 , , , 1234 1236 in in IN 1237 1243 NFATx1 NFATx1 NNP 1243 1244 . . . 1245 1247 We we PRP 1248 1252 have have VBP 1253 1259 mapped map VBN 1260 1263 the the DT 1264 1274 inhibitory inhibitory JJ 1275 1283 activity activity NN 1284 1286 to to TO 1287 1291 less less JJR 1292 1296 than than IN 1297 1299 60 60 CD 1300 1308 residues residue NNS 1308 1309 , , , 1310 1320 containing contain VBG 1321 1327 motifs motif NNS 1328 1332 that that WDT 1333 1336 are be VBP 1337 1346 conserved conserve VBN 1347 1349 in in IN 1350 1353 all all DT 1354 1358 NFAT nfat NN 1359 1367 proteins protein NNS 1367 1368 . . . 1369 1376 Finally finally RB 1376 1377 , , , 1378 1380 we we PRP 1381 1392 demonstrate demonstrate VBP 1393 1397 that that IN 1398 1406 deletion deletion NN 1407 1409 in in IN 1410 1416 NFATx1 nfatx1 NN 1417 1419 of of IN 1420 1423 the the DT 1424 1430 mapped map VBN 1431 1433 60 60 CD 1434 1442 residues residue NNS 1443 1448 leads lead VBZ 1449 1451 to to TO 1452 1455 its its PRP$ 1456 1463 nuclear nuclear JJ 1464 1477 translocation translocation NN 1478 1489 independent independent JJ 1490 1492 of of IN 1493 1500 calcium calcium NN 1501 1510 signaling signaling NN 1510 1511 . . . 1512 1515 Our our PRP$ 1516 1523 results result NNS 1524 1531 support support VBP 1532 1535 the the DT 1536 1541 model model NN 1542 1551 proposing propose VBG 1552 1556 that that IN 1557 1560 the the DT 1561 1571 N-terminal n-terminal JJ 1572 1578 domain domain NN 1579 1586 confers confer VBZ 1587 1604 calcium-signaling calcium-signaling JJ 1605 1615 dependence dependence NN 1616 1618 on on IN 1619 1625 NFATx1 nfatx1 NN 1626 1641 transactivation transactivation NN 1642 1650 activity activity NN 1651 1653 by by IN 1654 1664 regulating regulate VBG 1665 1668 its its PRP$ 1669 1682 intracellular intracellular JJ 1683 1695 localization localization NN 1696 1703 through through IN 1704 1705 a a DT 1706 1713 protein protein NN 1714 1720 module module NN 1721 1725 that that WDT 1726 1736 associates associate VBZ 1737 1741 with with IN 1742 1753 calcineurin calcineurin NN 1754 1757 and and CC 1758 1760 is be VBZ 1761 1762 a a DT 1763 1769 target target NN 1770 1772 of of IN 1773 1776 its its PRP$ 1777 1788 phosphatase phosphatase NN 1789 1797 activity activity NN 1797 1798 . . .