0 9 Molecular molecular JJ 10 13 and and CC 14 22 cellular cellular JJ 23 31 analysis analysis NN 32 34 of of IN 35 40 human human JJ 41 57 immunodeficiency immunodeficiency NN 58 71 virus-induced virus-induced JJ 72 81 apoptosis apoptosis NN 82 84 in in IN 85 99 lymphoblastoid lymphoblastoid JJ 100 122 T-cell-line-expressing t-cell-line-expressing JJ 123 132 wild-type wild-type JJ 133 136 and and CC 137 144 mutated mutate VBN 145 148 CD4 cd4 NN 149 158 receptors receptor NNS 158 159 . . . 161 163 We we PRP 164 168 have have VBP 169 179 previously previously RB 180 185 shown show VBN 186 190 that that IN 191 194 the the DT 195 203 presence presence NN 204 206 of of IN 207 210 the the DT 211 214 CD4 cd4 NN 215 226 cytoplasmic cytoplasmic JJ 227 231 tail tail NN 232 234 is be VBZ 235 243 critical critical JJ 244 247 for for IN 248 253 human human JJ 254 270 immunodeficiency immunodeficiency NN 271 276 virus virus NN 277 278 ( ( ( 278 290 HIV)-induced hiv)-induced JJ 291 300 apoptosis apoptosis NN 301 302 ( ( ( 302 311 J.Corbeil J.Corbeil NNP 311 312 , , , 313 323 M.Tremblay M.Tremblay NNP 323 324 , , , 325 328 and and CC 329 340 D.D.Richman D.D.Richman NNP 340 341 , , , 342 361 J.Exp.Med.183:39-48 j.exp.med.183:39-48 CD 361 362 , , , 363 367 1996 1996 CD 367 368 ) ) ) 368 369 . . . 370 372 We we PRP 373 377 have have VBP 378 385 pursued pursue VBN 386 389 our our PRP$ 390 403 investigation investigation NN 404 406 of of IN 407 410 the the DT 411 415 role role NN 416 418 of of IN 419 422 the the DT 423 426 CD4 cd4 NN 427 439 transduction transduction NN 440 447 pathway pathway NN 448 450 in in IN 451 462 HIV-induced hiv-induced JJ 463 472 apoptosis apoptosis NN 472 473 . . . 474 476 To to TO 477 479 do do VB 480 484 this this DT 484 485 , , , 486 495 wild-type wild-type JJ 496 499 and and CC 500 506 mutant mutant JJ 507 512 forms form NNS 513 515 of of IN 516 519 the the DT 520 523 CD4 cd4 NN 524 535 cytoplasmic cytoplasmic JJ 536 540 tail tail NN 541 545 were be VBD 546 552 stably stably RB 553 562 expressed express VBN 563 565 in in IN 566 569 the the DT 570 584 lymphoblastoid lymphoblastoid JJ 585 591 T-cell t-cell NN 592 596 line line NN 597 602 A2.01 a2.01 NN 602 603 . . . 604 613 Apoptosis Apoptosis NNP 614 617 was be VBD 618 627 prevented prevent VBN 628 632 when when WRB 633 636 CD4 cd4 NN 637 646 truncated truncate VBN 647 649 at at IN 650 657 residue residue NN 658 661 402 402 CD 662 665 was be VBD 666 675 expressed express VBN 675 676 ; ; : 677 684 however however RB 684 685 , , , 686 691 cells cell NNS 692 702 expressing express VBG 703 710 mutated mutate VBN 711 720 receptors receptor NNS 721 725 that that WDT 726 728 do do VBP 729 732 not not RB 733 742 associate associate VB 743 747 with with IN 748 756 p56(lck) p56(lck) NNP 757 758 ( ( ( 758 765 mutated mutate VBN 766 768 at at IN 769 772 the the DT 773 783 dicysteine dicysteine NN 784 789 motif motif NN 790 793 and and CC 794 803 truncated truncate VBN 804 806 at at IN 807 814 residue residue NN 815 818 418 418 CD 818 819 ) ) ) 820 823 but but CC 824 829 which which WDT 830 839 conserved conserve VBD 840 848 proximal proximal JJ 849 856 domains domain NNS 857 859 of of IN 860 863 the the DT 864 875 cytoplasmic cytoplasmic JJ 876 880 tail tail NN 881 890 underwent undergo VBD 891 900 apoptosis apoptosis NN 901 905 like like IN 906 911 wild- wild- JJ 912 916 type type NN 917 920 CD4 cd4 NN 920 921 . . . 922 925 The the DT 926 937 differences difference NNS 938 945 between between IN 946 955 wild-type wild-type JJ 956 959 and and CC 960 967 mutated mutate VBN 968 977 receptors receptor NNS 978 980 in in IN 981 984 the the DT 985 994 induction induction NN 995 997 of of IN 998 1007 apoptosis apoptosis NN 1008 1012 were be VBD 1013 1016 not not RB 1017 1024 related related JJ 1025 1027 to to TO 1028 1034 levels level NNS 1035 1037 of of IN 1038 1046 p56(lck) p56(lck) NNP 1047 1049 or or CC 1050 1053 NF- nf- NF- 1054 1060 kappaB kappab NN 1061 1071 activation activation NN 1071 1072 . . . 1073 1080 Initial initial JJ 1081 1090 signaling signaling NN 1091 1098 through through IN 1099 1102 the the DT 1103 1106 CD4 cd4 NN 1107 1115 receptor receptor NN 1116 1122 played play VBD 1123 1124 a a DT 1125 1130 major major JJ 1131 1135 role role NN 1136 1138 in in IN 1139 1142 the the DT 1143 1156 sensitization sensitization NN 1157 1159 of of IN 1160 1172 HIV-infected hiv-infected JJ 1173 1174 T t NN 1175 1180 cells cell NNS 1181 1183 to to TO 1184 1191 undergo undergo VB 1192 1201 apoptosis apoptosis NN 1201 1202 . . . 1203 1213 Incubation incubation NN 1214 1216 of of IN 1217 1229 HIV-infected hiv-infected JJ 1230 1235 cells cell NNS 1236 1240 with with IN 1241 1251 monoclonal monoclonal JJ 1252 1260 antibody antibody NN 1261 1262 ( ( ( 1262 1265 MAb MAb NNP 1265 1266 ) ) ) 1267 1273 13B8-2 13b8-2 NN 1273 1274 , , , 1275 1280 which which WDT 1281 1286 binds bind VBZ 1287 1289 to to TO 1290 1293 CD4 cd4 NN 1294 1296 in in IN 1297 1298 a a DT 1299 1305 region region NN 1306 1314 critical critical JJ 1315 1318 for for IN 1319 1331 dimerization dimerization NN 1332 1334 of of IN 1335 1338 the the DT 1339 1347 receptor receptor NN 1347 1348 , , , 1349 1358 prevented prevent VBD 1359 1368 apoptosis apoptosis NN 1369 1376 without without IN 1377 1387 inhibiting inhibit VBG 1388 1391 HIV HIV NNP 1392 1403 replication replication NN 1403 1404 . . . 1405 1413 Moreover moreover RB 1413 1414 , , , 1415 1418 the the DT 1419 1428 apoptotic apoptotic JJ 1429 1436 process process NN 1437 1440 was be VBD 1441 1444 not not RB 1445 1452 related related JJ 1453 1455 to to TO 1456 1463 Fas-Fas fas-fas JJ 1464 1470 ligand ligand NN 1471 1482 interaction interaction NN 1482 1483 ; ; : 1484 1491 however however RB 1491 1492 , , , 1493 1495 an an DT 1496 1508 antagonistic antagonistic JJ 1509 1517 anti-Fas anti-fas JJ 1518 1521 MAb MAb NNP 1522 1523 ( ( ( 1523 1527 ZB-4 zb-4 NN 1527 1528 ) ) ) 1529 1537 enhanced enhance VBD 1538 1547 apoptosis apoptosis NN 1548 1550 in in IN 1551 1563 HIV-infected hiv-infected JJ 1564 1569 cells cell NNS 1570 1577 without without IN 1578 1586 inducing induce VBG 1587 1596 apoptosis apoptosis NN 1597 1599 in in IN 1600 1610 uninfected uninfected JJ 1611 1616 cells cell NNS 1616 1617 . . . 1618 1623 These these DT 1624 1636 observations observation NNS 1637 1648 demonstrate demonstrate VBP 1649 1653 that that IN 1654 1657 CD4 cd4 NN 1658 1667 signaling signaling NN 1668 1676 mediates mediate VBZ 1677 1688 HIV-induced hiv-induced JJ 1689 1698 apoptosis apoptosis NN 1699 1701 by by IN 1702 1703 a a DT 1704 1713 mechanism mechanism NN 1714 1725 independent independent JJ 1726 1728 of of IN 1729 1736 Fas-Fas fas-fas JJ 1737 1743 ligand ligand NN 1744 1755 interaction interaction NN 1755 1756 , , , 1757 1761 does do VBZ 1762 1765 not not RB 1766 1773 require require VB 1774 1782 p56(lck) p56(lck) NN 1783 1792 signaling signaling NN 1792 1793 , , , 1794 1797 and and CC 1798 1801 may may MD 1802 1809 involve involve VB 1810 1811 a a DT 1812 1820 critical critical JJ 1821 1827 region region NN 1828 1831 for for IN 1832 1835 CD4 cd4 NN 1836 1848 dimerization dimerization NN 1848 1849 . . .