216:
to fight off tumors in the body. Studies have shown that the immune system even has the ability to prevent precancerous cells from growing and arbitrate the regression of established tumors. The dangerous thing about cancer cells is they have the ability to inhibit the function of the immune system. Although a tumor may be in its beginning stage and very weak, it may be giving off chemicals that inhibit the function of the immune system allowing it to grow and become harmful. Tests have shown that mice without granzymes and perforins are at high risk to have tumors spread throughout their body.
127:
cell types either do not express perforin or do not form immunological synapses, granzyme B is released extracellularly. Extracellular granzyme B can accumulate in the extracellular space in diseases associated with dysregulated or chronic inflammation leading to the degradation of extracellular matrix proteins and impaired tissue healing and remodelling. Extracellular granzyme B has been implicated in the pathogenesis of atherosclerosis, aneurysm, vascular leakage, chronic wound healing, and skin aging.
196:, or the job of maintaining homeostasis in the immune system during an infection. “In humans, loss of perforin function leads to a syndrome called familial hemophagocytic lymphohistiocytosis ”. This syndrome can lead to death because both T cells and macrophages multiply to fight the pathogen, resulting in harmful levels of proinflammatory cytokines. The overactivation can lead to inflammation of vital organs, anemia via overactivated macrophages phagocytosing blood cells, and can potentially be fatal.
203:'s paper he talks about how granzymes may have other functions, in addition to their ability to fight off infection. Granzyme A contains certain chemicals that allow it to cause proliferation in B cells to reduce the chance of cancer growth and formation. Test on mice have shown that granzyme A and B might not have a direct link to controlling viral infections, but helping accelerate the immune systems response.
1838:
55:. Granzymes can also be detected in the rough endoplasmic reticulum, golgi complex, and the trans-golgi reticulum. The contents of the cytotoxic granules function to permit entry of the granzymes into the target cell cytosol. The granules are released into an immune synapse formed with a target cell, where
179:
of swollen joints”. When granzymes are in an extracellular state they have the ability to activate macrophages and mast cells to initiate the inflammatory response. The interaction between the granzymes and somatic cells are still unexplainable but advances in understanding the process are being made
126:
More recently, in addition to T lymphocytes, granzymes have been shown to be expressed in other types of immune cells such as dendritic cells, B cells and mast cells. In addition, granzymes may also be expressed in non-immune cells such as keratinocytes, pneumocytes and chondrocytes. As many of these
223:. This inhibits proliferation and activation of T cells. TGF-β production is the most potent mechanism of immune avoidance used by tumors. TGF-β inhibits expression of five different cytotoxic genes including perforin, granzyme A, and granzyme B, which then inhibits T cell-mediated tumor clearance.
215:
the process whereby precancerous and malignant cells are recognized by the immune system as damaged and are consequently targeted for elimination”. For a tumor to progress it requires conditions within the body and surrounding area to be growth-promoting. Almost all people have suitable immune cells
122:
In addition to killing their target cells, granzymes can target and kill intracellular pathogens. Granzymes A and B induce lethal oxidative damage in bacteria by cleaving components of the electron transport chain, while granzyme B cleaves viral proteins to inhibit viral activation and replication.
139:
and his group published a paper on their discovery of granzymes. In the paper they discussed how they purified, characterized and discovered a variety of granzymes found within cytolytic granules that were carried by cytotoxic T lymphocytes and natural killer cells. Jürg was able to identify 8
118:
proteins (IAPs)), among other proteins. Granzyme B also cleaves many of the proteins responsible for apoptosis in the absence of caspase activity. The other granzymes activate cell death by caspase-dependent and caspase-independent mechanisms.
140:
different granzymes and discovered partial amino acid sequences for each. The molecules were unofficially named Grs for five years before Jürg and his team came up with the name granzymes which was widely accepted by the scientific community.
234:
did not have as big of a role in lymphoma surveillance as its counterpart perforin. Perforin and granzymes have been found to have a directly related ability to protect the body against the formation of different kinds of lymphomas.
188:
has been found to have a direct correlation with patients who have a viral infection. Scientists are able to conclude that granzyme H specializes in detecting ‘proteolytic degradation’ which is found in viral proteins.
63:
in the target cell, and finally into the target cell cytosol. Granzymes are part of the serine esterase family. They are closely related to other immune serine proteases expressed by innate immune cells, such as
876:
Hiebert PR, Boivin WA, Abraham T, Pazooki S, Zhao H, Granville DJ (June 2011). "Granzyme B contributes to extracellular matrix remodeling and skin aging in apolipoprotein E knockout mice".
1492:
1352:
175:
state. Granzymes have also been found to help initiate the inflammatory response. “For example, rheumatoid arthritis patients have increased levels of granzyme A in the
1092:
51:. Granzymes also kill bacteria and inhibit viral replication. In NK cells and T cells, granzymes are packaged in cytotoxic granules along with
91:
1085:
620:"Perforin and granzyme B have separate and distinct roles during atherosclerotic plaque development in apolipoprotein E knockout mice"
99:
1557:
1868:
1078:
123:
The granzymes bind directly to the nucleic acids DNA and RNA; this enhances their cleavage of nucleic acid binding proteins.
1713:
1020:
200:
1828:
444:"Leukocyte protease binding to nucleic acids promotes nuclear localization and cleavage of nucleic acid binding proteins"
1312:
493:"Granzyme B inhibits vaccinia virus production through proteolytic cleavage of eukaryotic initiation factor 4 gamma 3"
1070:
829:"Granzyme B degrades extracellular matrix and contributes to delayed wound closure in apolipoprotein E knockout mice"
780:"Granzyme B releases vascular endothelial growth factor from extracellular matrix and induces vascular permeability"
171:
has been known to be found in elevated levels within patients who currently have an infectious disease and/or in a
95:
1698:
1814:
1801:
1788:
1775:
1762:
1749:
1736:
1227:
1212:
1112:
1708:
1662:
1605:
1109:
1610:
1502:
1467:
1462:
87:
1863:
115:
24:
1631:
1550:
1457:
1307:
1703:
1447:
631:
1667:
1347:
1337:
1154:
1149:
212:
65:
32:
1858:
1600:
901:
679:"Perforin-independent extracellular granzyme B activity contributes to abdominal aortic aneurysm"
392:"Cytotoxic T lymphocyte granules are secretory lysosomes, containing both perforin and granzymes"
343:"Cytotoxic cells kill intracellular bacteria through granulysin-mediated delivery of granzymes"
1329:
1056:
1002:
950:
893:
858:
809:
760:
708:
659:
600:
565:
524:
473:
421:
372:
320:
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245:
1646:
1641:
1615:
1543:
1121:
1046:
1036:
992:
940:
932:
885:
848:
840:
799:
791:
750:
742:
698:
690:
649:
639:
592:
583:
Hiebert PR, Granville DJ (December 2012). "Granzyme B in injury, inflammation, and repair".
555:
514:
504:
463:
455:
411:
403:
362:
354:
310:
28:
1693:
1677:
1590:
1362:
1357:
1129:
1105:
219:
Tumors have the ability to escape from immune surveillance by secreting immunosuppressive
20:
159:. Alternatively, granzyme activity can be assayed by virtue of their protease activity.
136:
731:"Serpina3n accelerates tissue repair in a diabetic mouse model of delayed wound healing"
635:
1842:
1731:
1672:
945:
920:
853:
828:
804:
779:
755:
730:
703:
678:
654:
619:
519:
492:
468:
443:
416:
391:
367:
342:
176:
152:
1051:
1024:
1852:
1636:
1595:
1507:
1380:
1369:
1101:
1041:
905:
1585:
1403:
1297:
1139:
172:
144:
103:
211:
In Cullen's paper “Granzymes in Cancer and
Immunity” he describes the process of “
644:
596:
509:
1809:
1744:
1580:
1522:
1517:
1166:
889:
193:
102:
to change the membrane permeability of the mitochondria, causing the release of
69:
1837:
694:
358:
1484:
1426:
1207:
1202:
1182:
795:
111:
75:
459:
1783:
1757:
1512:
1498:
1317:
1197:
1187:
107:
83:
60:
36:
1060:
1006:
954:
897:
862:
813:
764:
746:
712:
663:
604:
569:
528:
477:
407:
376:
324:
425:
1398:
1342:
1192:
1177:
1144:
997:
980:
936:
542:
Hendel A, Hiebert PR, Boivin WA, Williams SJ, Granville DJ (April 2010).
227:
220:
151:
techniques. Granzyme secreting cells can be identified and quantified by
56:
52:
48:
844:
39:(apoptosis) in the target cell, thus eliminating cells that have become
1452:
1442:
1388:
1302:
1134:
560:
543:
156:
79:
491:
Marcet-Palacios M, Duggan BL, Shostak I, et al. (December 2011).
315:
298:
167:
In Cullen's paper “Granzymes in Cancer and
Immunity” he discusses how
1796:
1566:
1479:
1421:
192:
Cullen further states in his paper that granzymes may have a role in
40:
1770:
1488:
1474:
1413:
1287:
1282:
1277:
1272:
1267:
1262:
148:
44:
184:
have been found in high levels of patients who have gone septic.
1257:
1252:
1247:
1242:
1237:
1232:
1222:
1217:
677:
Chamberlain CM, Ang LS, Boivin WA, et al. (February 2010).
618:
Hiebert PR, Boivin WA, Zhao H, McManus BM, Granville DJ (2013).
544:"Granzymes in age-related cardiovascular and pulmonary diseases"
185:
181:
168:
1539:
1074:
231:
1025:"Granzymes: a family of lymphocyte granule serine proteases"
442:
Thomas MP, Whangbo J, McCrossan G, et al. (June 2014).
90:
to execute cell death. Granzyme B also cleaves the protein
1535:
390:
Peters PJ, Borst J, Oorschot V, et al. (May 1991).
341:
Walch M, Dotiwala F, Mulik S, et al. (June 2014).
143:
Granzyme secretion can be detected and measured using
1826:
1722:
1686:
1655:
1624:
1573:
1435:
1412:
1378:
1328:
1165:
1120:
729:Hsu I, Parkinson LG, Shen Y, et al. (2014).
114:), Smac/Diablo and Omi/HtrA2 (which suppress the
974:
972:
970:
968:
966:
964:
919:Ewen CL, Kane KP, Bleackley RC (January 2012).
827:Hiebert PR, Wu D, Granville DJ (October 2013).
724:
722:
230:was emphasized when scientists discovered that
226:Perforin's role in protecting the body against
106:(which is one of the parts needed to activate
1551:
1086:
979:Cullen SP, Brunet M, Martin SJ (April 2010).
8:
86:), which cleaves many substrates, including
59:mediates the delivery of the granzymes into
778:Hendel A, Hsu I, Granville DJ (July 2014).
292:
290:
1558:
1544:
1536:
1093:
1079:
1071:
1050:
1040:
996:
944:
852:
803:
754:
702:
653:
643:
559:
518:
508:
467:
415:
366:
314:
437:
435:
1833:
336:
334:
286:
1106:serine proteases/serine endopeptidases
7:
396:The Journal of Experimental Medicine
297:Bots M, Medema JP (December 2006).
981:"Granzymes in cancer and immunity"
78:activates apoptosis by activating
14:
683:The American Journal of Pathology
180:constantly. Other granzymes like
1836:
1042:10.1186/gb-2001-2-12-reviews3014
921:"A quarter century of granzymes"
985:Cell Death and Differentiation
925:Cell Death and Differentiation
833:Cell Death and Differentiation
548:Cell Death and Differentiation
94:, which recruits the proteins
1:
1318:Urinary plasminogen activator
1313:Tissue plasminogen activator
645:10.1371/journal.pone.0078939
597:10.1016/j.molmed.2012.09.009
585:Trends in Molecular Medicine
510:10.1371/journal.ppat.1002447
890:10.1016/j.exger.2011.02.004
1885:
695:10.2353/ajpath.2010.090700
359:10.1016/j.cell.2014.03.062
1714:Michaelis–Menten kinetics
1404:Proteinase 3/Myeloblastin
796:10.1038/labinvest.2014.62
1606:Diffusion-limited enzyme
878:Experimental Gerontology
784:Laboratory Investigation
735:Cell Death & Disease
460:10.4049/jimmunol.1303296
35:(NK) cells. They induce
23:released by cytoplasmic
303:Journal of Cell Science
299:"Granzymes at a glance"
88:caspase-activated DNase
1458:Proprotein convertases
747:10.1038/cddis.2014.423
408:10.1084/jem.173.5.1099
116:inhibitor of apoptosis
1869:Programmed cell death
1699:Eadie–Hofstee diagram
1632:Allosteric regulation
1308:Plasminogen activator
448:Journal of Immunology
43:or are infected with
37:programmed cell death
1709:Lineweaver–Burk plot
1448:Prolyl endopeptidase
998:10.1038/cdd.2009.206
937:10.1038/cdd.2011.153
1035:(12): REVIEWS3014.
845:10.1038/cdd.2013.96
636:2013PLoSO...878939H
213:immune surveillance
66:neutrophil elastase
1668:Enzyme superfamily
1601:Enzyme promiscuity
561:10.1038/cdd.2010.5
207:In cancer research
1824:
1823:
1533:
1532:
1330:Complement system
1122:Digestive enzymes
316:10.1242/jcs.03239
309:(Pt 24): 5011–4.
29:cytotoxic T cells
1876:
1841:
1840:
1832:
1704:Hanes–Woolf plot
1647:Enzyme activator
1642:Enzyme inhibitor
1616:Enzyme catalysis
1560:
1553:
1546:
1537:
1095:
1088:
1081:
1072:
1065:
1064:
1054:
1044:
1017:
1011:
1010:
1000:
976:
959:
958:
948:
916:
910:
909:
873:
867:
866:
856:
824:
818:
817:
807:
775:
769:
768:
758:
726:
717:
716:
706:
674:
668:
667:
657:
647:
615:
609:
608:
580:
574:
573:
563:
539:
533:
532:
522:
512:
503:(12): e1002447.
488:
482:
481:
471:
439:
430:
429:
419:
387:
381:
380:
370:
338:
329:
328:
318:
294:
194:immunomodulation
173:pro-inflammatory
21:serine proteases
1884:
1883:
1879:
1878:
1877:
1875:
1874:
1873:
1849:
1848:
1847:
1835:
1827:
1825:
1820:
1732:Oxidoreductases
1718:
1694:Enzyme kinetics
1682:
1678:List of enzymes
1651:
1620:
1591:Catalytic triad
1569:
1564:
1534:
1529:
1431:
1408:
1374:
1324:
1161:
1130:Enteropeptidase
1116:
1099:
1069:
1068:
1019:
1018:
1014:
978:
977:
962:
918:
917:
913:
875:
874:
870:
839:(10): 1404–14.
826:
825:
821:
777:
776:
772:
728:
727:
720:
676:
675:
671:
617:
616:
612:
582:
581:
577:
541:
540:
536:
490:
489:
485:
441:
440:
433:
402:(5): 1099–109.
389:
388:
384:
340:
339:
332:
296:
295:
288:
283:
241:
209:
165:
163:Other functions
133:
12:
11:
5:
1882:
1880:
1872:
1871:
1866:
1861:
1851:
1850:
1846:
1845:
1822:
1821:
1819:
1818:
1805:
1792:
1779:
1766:
1753:
1740:
1726:
1724:
1720:
1719:
1717:
1716:
1711:
1706:
1701:
1696:
1690:
1688:
1684:
1683:
1681:
1680:
1675:
1670:
1665:
1659:
1657:
1656:Classification
1653:
1652:
1650:
1649:
1644:
1639:
1634:
1628:
1626:
1622:
1621:
1619:
1618:
1613:
1608:
1603:
1598:
1593:
1588:
1583:
1577:
1575:
1571:
1570:
1565:
1563:
1562:
1555:
1548:
1540:
1531:
1530:
1528:
1527:
1526:
1525:
1520:
1510:
1505:
1496:
1482:
1477:
1472:
1471:
1470:
1465:
1455:
1450:
1445:
1439:
1437:
1433:
1432:
1430:
1429:
1424:
1418:
1416:
1410:
1409:
1407:
1406:
1401:
1396:
1391:
1385:
1383:
1376:
1375:
1373:
1372:
1367:
1366:
1365:
1360:
1350:
1345:
1340:
1334:
1332:
1326:
1325:
1323:
1322:
1321:
1320:
1315:
1305:
1293:
1292:
1291:
1290:
1285:
1280:
1275:
1270:
1265:
1260:
1255:
1250:
1245:
1240:
1235:
1230:
1225:
1220:
1215:
1205:
1200:
1195:
1190:
1185:
1180:
1171:
1169:
1163:
1162:
1160:
1159:
1158:
1157:
1152:
1142:
1137:
1132:
1126:
1124:
1118:
1117:
1102:Endopeptidases
1100:
1098:
1097:
1090:
1083:
1075:
1067:
1066:
1029:Genome Biology
1012:
960:
911:
868:
819:
770:
718:
689:(2): 1038–49.
669:
630:(10): e78939.
610:
591:(12): 732–41.
575:
554:(4): 596–606.
534:
497:PLOS Pathogens
483:
454:(11): 5390–7.
431:
382:
353:(6): 1309–23.
330:
285:
284:
282:
279:
278:
277:
270:
263:
256:
249:
240:
237:
208:
205:
177:synovial fluid
164:
161:
153:flow cytometry
132:
129:
33:natural killer
13:
10:
9:
6:
4:
3:
2:
1881:
1870:
1867:
1865:
1864:Immune system
1862:
1860:
1857:
1856:
1854:
1844:
1839:
1834:
1830:
1816:
1812:
1811:
1806:
1803:
1799:
1798:
1793:
1790:
1786:
1785:
1780:
1777:
1773:
1772:
1767:
1764:
1760:
1759:
1754:
1751:
1747:
1746:
1741:
1738:
1734:
1733:
1728:
1727:
1725:
1721:
1715:
1712:
1710:
1707:
1705:
1702:
1700:
1697:
1695:
1692:
1691:
1689:
1685:
1679:
1676:
1674:
1673:Enzyme family
1671:
1669:
1666:
1664:
1661:
1660:
1658:
1654:
1648:
1645:
1643:
1640:
1638:
1637:Cooperativity
1635:
1633:
1630:
1629:
1627:
1623:
1617:
1614:
1612:
1609:
1607:
1604:
1602:
1599:
1597:
1596:Oxyanion hole
1594:
1592:
1589:
1587:
1584:
1582:
1579:
1578:
1576:
1572:
1568:
1561:
1556:
1554:
1549:
1547:
1542:
1541:
1538:
1524:
1521:
1519:
1516:
1515:
1514:
1511:
1509:
1508:Streptokinase
1506:
1504:
1500:
1497:
1494:
1490:
1486:
1483:
1481:
1478:
1476:
1473:
1469:
1466:
1464:
1461:
1460:
1459:
1456:
1454:
1451:
1449:
1446:
1444:
1441:
1440:
1438:
1434:
1428:
1425:
1423:
1420:
1419:
1417:
1415:
1411:
1405:
1402:
1400:
1397:
1395:
1392:
1390:
1387:
1386:
1384:
1382:
1381:immune system
1377:
1371:
1370:C3-convertase
1368:
1364:
1361:
1359:
1356:
1355:
1354:
1351:
1349:
1346:
1344:
1341:
1339:
1336:
1335:
1333:
1331:
1327:
1319:
1316:
1314:
1311:
1310:
1309:
1306:
1304:
1301:
1299:
1295:
1294:
1289:
1286:
1284:
1281:
1279:
1276:
1274:
1271:
1269:
1266:
1264:
1261:
1259:
1256:
1254:
1251:
1249:
1246:
1244:
1241:
1239:
1236:
1234:
1231:
1229:
1226:
1224:
1221:
1219:
1216:
1214:
1211:
1210:
1209:
1206:
1204:
1201:
1199:
1196:
1194:
1191:
1189:
1186:
1184:
1181:
1179:
1176:
1173:
1172:
1170:
1168:
1164:
1156:
1153:
1151:
1148:
1147:
1146:
1143:
1141:
1138:
1136:
1133:
1131:
1128:
1127:
1125:
1123:
1119:
1114:
1111:
1107:
1103:
1096:
1091:
1089:
1084:
1082:
1077:
1076:
1073:
1062:
1058:
1053:
1048:
1043:
1038:
1034:
1030:
1026:
1022:
1016:
1013:
1008:
1004:
999:
994:
991:(4): 616–23.
990:
986:
982:
975:
973:
971:
969:
967:
965:
961:
956:
952:
947:
942:
938:
934:
930:
926:
922:
915:
912:
907:
903:
899:
895:
891:
887:
884:(6): 489–99.
883:
879:
872:
869:
864:
860:
855:
850:
846:
842:
838:
834:
830:
823:
820:
815:
811:
806:
801:
797:
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790:(7): 716–25.
789:
785:
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774:
771:
766:
762:
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748:
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741:(10): e1458.
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736:
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723:
719:
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34:
30:
26:
22:
18:
1810:Translocases
1807:
1794:
1781:
1768:
1755:
1745:Transferases
1742:
1729:
1586:Binding site
1393:
1298:fibrinolysis
1296:
1174:
1140:Chymotrypsin
1032:
1028:
1015:
988:
984:
931:(1): 28–35.
928:
924:
914:
881:
877:
871:
836:
832:
822:
787:
783:
773:
738:
734:
686:
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672:
627:
623:
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306:
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272:
265:
258:
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244:
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218:
210:
198:
191:
166:
145:Western Blot
142:
137:Jürg Tschopp
134:
125:
121:
104:cytochrome c
82:(especially
74:
16:
15:
1581:Active site
1203:Factor XIIa
1183:Factor VIIa
1167:Coagulation
70:cathepsin G
1853:Categories
1784:Isomerases
1758:Hydrolases
1625:Regulation
1485:Subtilisin
1427:Batroxobin
1208:Kallikrein
1198:Factor XIa
1188:Factor IXa
1155:Pancreatic
1150:Neutrophil
1021:Trapani JA
281:References
186:Granzyme H
182:granzyme K
169:granzyme A
112:apoptosome
76:Granzyme B
1859:EC 3.4.21
1663:EC number
1513:Cathepsin
1499:Sedolisin
1475:Prostasin
1193:Factor Xa
108:caspase-9
84:caspase-3
61:endosomes
41:cancerous
17:Granzymes
1687:Kinetics
1611:Cofactor
1574:Activity
1414:Venombin
1399:Tryptase
1394:Granzyme
1348:Factor I
1343:Factor D
1338:Factor B
1178:Thrombin
1175:factors:
1145:Elastase
1061:11790262
1023:(2001).
1007:20075940
955:22052191
906:33176028
898:21316440
863:23912712
814:24791744
765:25299783
713:20035050
664:24205352
624:PLOS ONE
605:23099058
570:20139894
529:22194691
478:24771851
377:24906149
325:17158907
228:lymphoma
135:In 1986
110:via the
80:caspases
57:perforin
53:perforin
49:bacteria
25:granules
1843:Biology
1797:Ligases
1567:Enzymes
1453:Pronase
1443:Acrosin
1389:Chymase
1303:Plasmin
1135:Trypsin
946:3252830
854:3770318
805:4074428
756:4237249
704:2808106
655:3811993
632:Bibcode
520:3240606
469:4041364
426:2022921
417:2118839
368:4090916
201:Trapani
157:ELISPOT
131:History
45:viruses
27:within
1829:Portal
1771:Lyases
1480:Reelin
1422:Ancrod
1379:Other
1113:3.4.21
1059:
1052:138995
1049:
1005:
953:
943:
904:
896:
861:
851:
812:
802:
763:
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711:
701:
662:
652:
603:
568:
527:
517:
476:
466:
424:
414:
375:
365:
323:
1723:Types
1489:Furin
1436:Other
1363:MASP2
1358:MASP1
1288:KLK15
1283:KLK14
1278:KLK13
1273:KLK12
1268:KLK11
1263:KLK10
902:S2CID
239:Genes
221:TGF-β
149:ELISA
1815:list
1808:EC7
1802:list
1795:EC6
1789:list
1782:EC5
1776:list
1769:EC4
1763:list
1756:EC3
1750:list
1743:EC2
1737:list
1730:EC1
1503:TPP1
1353:MASP
1258:KLK9
1253:KLK8
1248:KLK7
1243:KLK6
1238:KLK5
1233:KLK4
1228:KLK3
1223:KLK2
1218:KLK1
1057:PMID
1003:PMID
951:PMID
894:PMID
859:PMID
810:PMID
761:PMID
709:PMID
660:PMID
601:PMID
566:PMID
525:PMID
474:PMID
422:PMID
373:PMID
347:Cell
321:PMID
274:GZMM
267:GZMK
260:GZMH
253:GZMB
246:GZMA
98:and
68:and
31:and
19:are
1493:S1P
1213:PSA
1047:PMC
1037:doi
993:doi
941:PMC
933:doi
886:doi
849:PMC
841:doi
800:PMC
792:doi
751:PMC
743:doi
699:PMC
691:doi
687:176
650:PMC
640:doi
593:doi
556:doi
515:PMC
505:doi
464:PMC
456:doi
452:192
412:PMC
404:doi
400:173
363:PMC
355:doi
351:157
311:doi
307:119
232:p53
199:In
155:or
147:or
100:Bak
96:Bax
92:Bid
47:or
1855::
1110:EC
1104::
1055:.
1045:.
1031:.
1027:.
1001:.
989:17
987:.
983:.
963:^
949:.
939:.
929:19
927:.
923:.
900:.
892:.
882:46
880:.
857:.
847:.
837:20
835:.
831:.
808:.
798:.
788:94
786:.
782:.
759:.
749:.
737:.
733:.
721:^
707:.
697:.
685:.
681:.
658:.
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626:.
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589:18
587:.
564:.
552:17
550:.
546:.
523:.
513:.
499:.
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472:.
462:.
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446:.
434:^
420:.
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398:.
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371:.
361:.
349:.
345:.
333:^
319:.
305:.
301:.
289:^
72:.
1831::
1817:)
1813:(
1804:)
1800:(
1791:)
1787:(
1778:)
1774:(
1765:)
1761:(
1752:)
1748:(
1739:)
1735:(
1559:e
1552:t
1545:v
1523:G
1518:A
1501:/
1495:4
1491:/
1487:/
1468:2
1463:1
1300::
1115:)
1108:(
1094:e
1087:t
1080:v
1063:.
1039::
1033:2
1009:.
995::
957:.
935::
908:.
888::
865:.
843::
816:.
794::
767:.
745::
739:5
715:.
693::
666:.
642::
634::
628:8
607:.
595::
572:.
558::
531:.
507::
501:7
480:.
458::
428:.
406::
379:.
357::
327:.
313::
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