Direct Cleavage by the Calcium-activated Protease Calpain Can Lead to Inactivation of Caspases

Name: Work Video:
Duration: 3 min 30 s
Boon Tin Chua; Ke Guo; Peng Li
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176], 'apoptosis': [16, 156, 178, 318, 344, 384, 426, 460, 495, 1115, 3340, 3640, 3741, 3813, 3830, 3923, 3959], 'can': [17, 87, 179, 249, 524, 1016, 1075, 2082, 2413, 2613, 2871, 2995], 'be': [18, 89, 180, 251, 525, 1017, 1076, 2083, 2264, 2414, 2614, 2779, 2872, 3198, 3218, 3379, 3654, 3836, 3930], 'sub-grouped': [19, 181], 'according': [20, 182, 530, 1337], 'to': [21, 37, 43, 121, 183, 199, 205, 283, 425, 458, 531, 550, 704, 987, 1061, 1097, 1113, 1168, 1338, 1413, 1469, 1475, 1486, 1519, 1526, 1618, 1687, 1784, 1894, 1917, 1934, 2152, 2204, 2233, 2263, 2294, 2400, 2477, 2636, 2699, 2810, 2851, 2929, 2998, 3105, 3217, 3381, 3467, 3500, 3565, 3638, 3804, 3835, 3999], 'length': [23, 185, 533], 'their': [25, 187, 535, 2125], 'prodomain.': [26, 188], 'Long': [27, 189], 'prodomain': [28, 47, 190, 209, 718, 757, 2298, 2328, 2523, 2776, 3661], 'caspases': [29, 42, 48, 60, 191, 204, 210, 222, 554, 585, 871, 1015, 1074, 1383, 2009, 2329, 3196, 3229, 3237, 3293, 3393, 3424, 3540, 3928], 'such': [30, 49, 192, 211, 431, 2330, 3268, 3363, 3425, 3541, 3851, 3916], 'as': [31, 40, 50, 61, 149, 193, 202, 212, 223, 311, 432, 489, 552, 700, 1050, 1309, 1346, 1529, 1636, 1804, 2331, 2416, 2541, 2644, 2710, 3142, 3163, 3238, 3269, 3324, 3364, 3426, 3542, 3554, 3632, 3852, 3917], 'caspase-8': [32, 194, 2332, 2341, 2377, 3427], 'caspase-9': [34, 86, 99, 112, 117, 131, 196, 248, 261, 274, 279, 293, 616, 711, 720, 759, 1093, 1319, 1609, 1631, 1762, 2334, 2343, 2379, 2393, 2398, 2424, 2452, 2502, 2520, 2577, 2588, 2612, 2640, 2673, 2739, 2753, 2770, 2773, 2898, 2917, 2935, 2994, 3002, 3015, 3069, 3429, 3441, 3477, 3490, 3561, 3566, 3597, 3614, 3663, 3671], 'are': [35, 197, 482, 487, 548, 775, 844, 991, 2010, 2128, 2150, 3282, 3294, 3394, 3545, 3556, 3603, 3997], 'believed': [36, 198, 549, 890], 'act': [38, 148, 200, 310, 551], 'mainly': [39, 201], 'upstream': [41, 78, 160, 203, 240, 322, 553, 3927], 'cleave': [44, 69, 206, 231, 2206], 'downstream': [45, 207], 'short': [46, 208], 'caspases-3': [51, 213, 2299], '-7.': [53, 215], 'We': [54, 216, 2062, 2761, 3092, 3300, 3344, 3388, 3606, 3892, 3982, 3996, 4032], 'report': [55, 217], 'here': [56, 218, 1013, 3096, 3391, 3894], 'identification': [58, 220], 'direct': [62, 128, 224, 290, 996, 2067, 3012, 3295, 3395, 3975], 'substrates': [63, 225, 915, 3297, 3396], 'calcium-activated': [65, 227], 'proteases,': [66, 228], 'calpains.': [67, 93, 229, 255, 3398, 3650], 'Calpains': [68, 230, 774], 'caspase-7': [70, 232, 1914, 1930, 1969, 1978, 2013, 2033, 2074, 2107, 2172, 2207, 2225, 2270, 3067, 3401], 'at': [71, 233, 878, 1279, 1449, 1512, 2023, 2044, 2309, 2503, 2512, 2526, 2562, 2606, 2618, 2766, 3082, 3458, 3491], 'sites': [72, 97, 234, 259, 1085, 2553, 3439], 'distinct': [73, 235], 'from': [74, 236, 1129, 1142, 1151, 1673, 1948, 2419, 3336, 4003, 4011], 'those': [75, 237], 'caspases,': [79, 241], 'generating': [80, 242, 2361, 3559], 'proteolytically': [81, 243, 1973], 'inactive': [82, 244, 490, 1974, 3421, 3613], 'fragments.': [83, 245, 2364, 3422], 'Caspase-8': [84, 246], 'also': [88, 250, 2292, 2303, 2338, 3094, 3158, 3262, 3345, 3431, 3607, 4033], 'directly': [90, 252, 1077, 2205], 'cleaved': [91, 108, 253, 270, 1018, 1078, 1765, 2304, 2345, 2435, 2501, 2615, 2704, 2723, 2919, 3080, 3432], 'by': [92, 103, 113, 132, 157, 254, 265, 275, 294, 319, 353, 386, 617, 716, 846, 859, 1019, 1079, 1094, 1116, 1232, 1301, 1348, 1484, 1531, 1638, 1679, 1683, 1697, 1746, 1751, 1806, 1982, 1990, 2085, 2238, 2305, 2335, 2346, 2380, 2448, 2543, 2579, 2590, 2616, 2632, 2641, 2659, 2678, 2705, 2712, 2754, 2874, 2920, 3016, 3201, 3305, 3353, 3357, 3402, 3433, 3461, 3547, 3563, 3641, 3664, 3676, 3752, 3831, 3857, 3924, 3960], 'Two': [94, 256, 795, 1081, 3436], 'calpain': [95, 114, 133, 257, 276, 295, 893, 914, 999, 1043, 1065, 1083, 1095, 1510, 1574, 1628, 1775, 2093, 2120, 2165, 2194, 2223, 2248, 2261, 2307, 2336, 2352, 2427, 2551, 2580, 2591, 2617, 2633, 2654, 2670, 2682, 2695, 2706, 2755, 2764, 2802, 2831, 2846, 2867, 2878, 2880, 2904, 2921, 2969, 2982, 2991, 3017, 3042, 3056, 3074, 3098, 3107, 3118, 3135, 3138, 3146, 3155, 3182, 3187, 3190, 3209, 3212, 3224, 3245, 3259, 3296, 3303, 3354, 3383, 3403, 3434, 3437, 3447, 3462, 3474, 3610, 3628, 3665, 3739, 3811, 3832, 3904, 3972, 4024], 'cleavage': [96, 129, 258, 291, 880, 894, 1048, 1067, 1084, 1944, 1952, 1970, 2014, 2075, 2108, 2173, 2237, 2256, 2271, 2325, 2375, 2390, 2479, 2533, 2552, 2571, 2578, 2589, 2605, 2624, 2631, 2671, 2743, 2751, 2765, 2819, 2870, 2992, 3013, 3111, 3162, 3194, 3227, 3249, 3257, 3320, 3352, 3438, 3448, 3454, 3471, 3475, 3488, 3602, 3611, 3658, 3907, 3925, 3976], 'have': [100, 262, 336, 455, 798, 916, 1086, 2930, 3093, 3389], 'been': [101, 263, 337, 456, 799, 917, 1005, 1087, 2123, 3743], 'identified': [102, 264, 800, 918, 1088, 3443], 'N-terminal': [104, 266, 536, 2449, 2462], 'sequencing': [105, 267, 2457], 'products.': [109, 271], 'Cleavage': [110, 272, 1091, 1928, 1976, 2511, 2525, 3064, 3399, 3457], 'generates': [115, 277, 1045, 2771, 3463, 3612], 'truncated': [116, 278, 2519, 2772], 'that': [118, 145, 280, 307, 486, 872, 891, 989, 1014, 1037, 1073, 1966, 2005, 2080, 2164, 2234, 2287, 2499, 2542, 2550, 2604, 2732, 2750, 2763, 2916, 2990, 3039, 3097, 3117, 3154, 3292, 3302, 3347, 3392, 3468, 3487, 3609, 3808, 3895, 3942, 3956], 'is': [119, 281, 586, 714, 857, 889, 896, 985, 1040, 2167, 2406, 2475, 2609, 2744, 2918, 3046, 3120, 3157, 3321, 3629, 3668, 3802, 3833, 3844, 3966], 'unable': [120, 282], 'activate': [122, 284, 1527, 3382], 'caspase-3': [123, 139, 285, 301, 1104, 1528, 2478, 2532, 2544, 2623, 2643, 2700, 2742, 2790, 2818, 2861, 2869, 2926, 2971, 3009, 3453, 3470, 3543, 3601, 3620], 'cell': [125, 287, 347, 360, 429, 1196, 1305, 1391, 1501, 1919, 2090, 2274, 2665, 2676, 2798, 2823, 3266, 3365, 3585, 3837], 'lysates.': [126, 288], 'Furthermore,': [127, 289], 'blocks': [134, 296, 3616, 3812], 'dATP': [135, 297, 602, 1101, 1523, 1949, 2660, 2728, 2787, 2814, 2855, 3006, 3571], 'cytochrome-c': [137, 299, 770, 1525, 2662, 2857, 3573, 3617], 'induced': [138, 300, 385, 3902], 'activation.': [140, 302, 2701, 2791, 3221, 3483, 3919], 'Therefore': [141, 303, 2260, 3827], 'our': [142, 304, 2160, 3285], 'results': [143, 305, 3281], 'suggest': [144, 306, 1072, 1109, 2004, 2163, 2498, 2989, 3291, 3486, 3955], 'calpains': [146, 308, 797, 856, 882, 990, 2070, 2081, 2129, 2500, 3165], 'may': [147, 309, 2291, 2778, 3378, 3497, 3653, 3929], 'negative': [150, 312], 'regulators': [151, 313], 'caspase': [153, 315, 703, 1001, 1121, 1993, 2383, 3110, 3161, 3239, 3248, 3256, 3308, 3319, 3351, 3918], 'processing': [154, 316], 'effectively': [158, 320], 'inactivating': [159, 321], 'caspases.': [161, 323, 1069, 3981], 'dithiothreitol': [324], 'phenylmethylsulfonyl': [325], 'fluoride': [326], 'polyacrylamide': [327], 'gel': [328, 1700], 'electrophoresis': [329], 'Alterations': [330], 'intracellular': [332, 777, 1117, 3645, 3939], 'calcium': [333, 1118, 2848, 3175], '(Ca2+)': [334], 'homeostasis': [335], 'implicated': [338], 'both': [339, 356, 865, 1567, 2148, 2199, 3066, 3164], 'promoting': [341], 'or': [342, 1403, 1862, 2847, 3913, 3949], 'inhibiting': [343], 'many': [346], 'types.': [348], 'An': [349], 'overload': [350], 'Ca2+': [352, 381, 453, 849, 860, 1058, 1925, 2432, 2808, 2836, 2906, 3028, 3376, 3581, 3842, 3896, 3940, 3964], 'excitotoxicity': [354], 'induces': [355], 'necrotic': [357], 'apoptotic': [359], 'death': [361], '(1.McGinnis': [362], 'K.M.': [363, 442], 'Wang': [364, 627, 651, 679, 739, 1364, 1547, 1654, 1822, 3692, 4010], 'K.W.': [365], 'Gnegy': [366], 'M.E.': [367, 440], 'J.': [368, 394, 438, 472, 499, 558, 624, 787, 808, 905, 947, 2051, 2137, 2940, 3523, 3720, 3777, 3820], 'Neurochem.': [369], '1999;': [370, 950, 3792, 3884], '72:': [371], '1853-1863Crossref': [372], 'PubMed': [373, 418, 448, 476, 505, 518, 564, 577, 638, 662, 690, 750, 831, 931, 958, 977, 1375, 1558, 1603, 1665, 1833, 2057, 2946, 2959, 3703, 3795, 3887], 'Scopus': [374, 419, 449, 477, 506, 519, 565, 578, 639, 663, 691, 751, 791, 812, 832, 909, 932, 959, 978, 1376, 1559, 1604, 1666, 1834, 2058, 2141, 2947, 2960, 3534, 3704, 3731, 3796, 3888], '(78)': [375], 'Google': [376, 399, 421, 451, 479, 508, 521, 567, 580, 641, 665, 693, 753, 793, 814, 834, 911, 934, 961, 980, 1378, 1561, 1606, 1668, 1836, 2060, 2143, 2949, 2962, 3536, 3706, 3733, 3798, 3825, 3890], 'Scholar).': [377, 452, 480, 522, 581, 694, 754, 794, 912, 981, 1379, 1562, 1607, 1669, 1837, 2061, 2144, 3537, 3734, 3799, 3826, 3891], 'Chelation': [378], 'extracellular': [380], 'protects': [382], 'against': [383, 3205], 'glucocorticoids': [387], 'thymocytes': [389, 3815], '(2.Squier': [390, 3816], 'M.K.T.': [391, 3817], 'Cohen': [392, 3818], 'J.J.': [393, 3819], 'Immunol.': [395, 3821], '1997;': [396, 654, 682, 742, 788, 809, 906, 928, 1367, 1550, 1657, 1825, 2138, 3695, 3822], '158:': [397, 3823], '3690-3697PubMed': [398, 3824], 'Scholar,': [400, 509, 568, 642, 666, 815, 2950, 3707], '3.Zhivotovsky': [401], 'B.': [402, 404], 'Cedervall': [403], 'Jiang': [405], 'S.': [406, 410, 783, 804, 821, 901, 940, 970, 1593, 2133, 3759, 3870], 'Nicotera': [407], 'P.': [408, 668, 728, 1353, 1536, 1643, 1811, 3681, 3785], 'Orrenius': [409, 969], 'Biochem.': [411, 786, 807, 904, 2136], 'Biophys.': [412], 'Res.': [413], 'Commun.': [414], '1994;': [415], '202:': [416], '120-127Crossref': [417], '(74)': [420], 'Scholar)': [422], 'but': [423, 1988, 3419], 'leads': [424, 1060, 1096], 'other': [428, 1145, 2007, 2157, 2288, 3265, 3374, 3539, 3911], 'types': [430, 3267], 'cultured': [434], 'neuronal': [435, 3947], 'cells': [436, 464, 1056, 1165, 1229, 1276, 3026, 3045, 3272, 3276, 3328, 3335, 3362, 3901, 3948], '(4.Tong': [437], 'Eichler': [439], 'Rich': [441], 'Exp.': [443], 'Neurol.': [444], '1996;': [445, 630], '138:': [446], '45-52Crossref': [447], '(41)': [450], 'ionophores': [454, 3377], 'shown': [457, 2211, 2685, 3095, 3216, 3390, 3744], 'inhibit': [459, 2860], 'interleukin-3-dependent': [462], 'hemopoietic': [463], '(5.Rodriguez-Tarduchy': [465], 'G.': [466, 3775, 3789], 'Collins': [467], 'M.': [468, 676, 736, 1361, 1544, 1651, 1819, 3689, 3761], 'Lopez-Rivas': [469], 'A.': [470, 650, 968], 'EMBO': [471], '1990;': [473], '9:': [474], '2997-3002Crossref': [475], '(207)': [478], 'Caspases': [481, 523], 'synthesized': [488], 'precursors': [491], 'activated': [493, 587, 2084, 3058, 3546], 'during': [494, 3220, 3944], '(6.Cryns': [496, 555, 2048, 2937], 'V.': [497, 556, 2049, 2938], 'Yuan': [498, 557, 2050, 2939], 'Genes': [500, 559, 2052, 2941], 'Dev.': [501, 560, 2053, 2942], '1998;': [502, 515, 561, 574, 974, 2054, 2943, 2956, 3526, 3723], '12:': [503, 562, 2055, 2944], '1551-1570Crossref': [504, 563, 2056, 2945], '(1160)': [507, 566, 2059, 2948], '7.Thornberry': [510, 569, 2951], 'N.A.': [511, 570, 2952], 'Lazebnik': [512, 571, 2953], 'Y.': [513, 572, 938, 2954, 3872], 'Science.': [514, 573, 2955, 3883], '281:': [516, 575, 2957], '1312-1322Crossref': [517, 576, 2958], '(6182)': [520, 579, 2961], 'classified': [526], 'into': [527, 1292, 1613, 2226], 'two': [528, 2504], 'subclasses': [529], 'prodomains.': [537], 'Caspases-1,': [538], '-2,': [539], '-8,': [540], '-9,': [541], '-10,': [543], 'which': [544, 612, 843, 1565, 1912, 1953, 2445, 2474, 3214, 3414, 3544], 'contain': [545], 'long': [546, 2327], 'prodomains,': [547], 'This': [582, 3651, 3800], 'class': [583], 'through': [588, 1235, 3969], 'interaction': [589, 607, 709, 3589], 'with': [590, 1029, 1057, 1178, 1191, 1216, 1266, 1386, 1420, 1494, 1505, 1704, 1735, 1881, 1936, 2036, 2092, 2426, 2547, 2800, 2827, 3073, 3076, 3284, 3329, 3451, 3507, 3678, 3934], 'specific': [591, 874, 1082, 3203], 'adapter': [592], 'proteins.': [593], 'In': [594], 'case': [596, 3576], 'caspase-9,': [598, 611, 3504, 3595, 3909, 4030], 'presence': [600, 1025, 1395, 1768, 1923, 2017, 2179, 2217, 2358, 2430, 2690, 2726, 2806, 2834, 2902, 2980, 3569], 'cytochrome-cwill': [604], 'initiate': [605], 'between': [608, 710, 998, 3590], 'Apaf-1': [609, 713, 726, 3679, 4028], 'turn': [614], 'activates': [615], 'autocatalysis': [618], '(8.Liu': [619], 'X.': [620, 628, 648, 652, 680, 740, 1365, 1548, 1655, 1823, 3693], 'Kim': [621], 'C.N.': [622], 'Yang': [623], 'Jemmerson': [625], 'R.': [626, 3773], 'Cell.': [629, 653, 681, 741, 926, 1366, 1549, 1656, 1824, 3694], '86:': [631], '147-157Abstract': [632], 'Full': [633, 635, 657, 659, 685, 687, 745, 747, 953, 955, 1370, 1372, 1553, 1555, 1660, 1662, 1828, 1830, 3529, 3531, 3698, 3700, 3726, 3728], 'Text': [634, 636, 658, 660, 686, 688, 746, 748, 954, 956, 1371, 1373, 1554, 1556, 1661, 1663, 1829, 1831, 3530, 3532, 3699, 3701, 3727, 3729], 'PDF': [637, 661, 689, 749, 957, 1374, 1557, 1664, 1832, 3533, 3702, 3730], '(4484)': [640], '9.Zou': [643], 'H.': [644, 781, 802, 899, 2131], 'Henzel': [645], 'W.J.': [646], 'Liu': [647], 'Lutschg': [649], '90:': [655], '405-413Abstract': [656], '(2746)': [664], '10.Li': [667], 'Nijhawan': [669, 729, 1354, 1537, 1644, 1812, 3682], 'D.': [670, 730, 1355, 1538, 1645, 1813, 3683], 'Budihardjo': [671, 731, 1356, 1539, 1646, 1814, 3684], 'I.': [672, 732, 942, 1357, 1540, 1647, 1815, 3183, 3685, 3763], 'Srinivasula': [673, 733, 1358, 1541, 1648, 1816, 3686], 'S.M.': [674, 734, 1359, 1542, 1649, 1817, 3687], 'Ahmad': [675, 735, 1360, 1543, 1650, 1818, 3688], 'Alnemri': [677, 737, 1362, 1545, 1652, 1820, 3690], 'E.S.': [678, 738, 1363, 1546, 1653, 1821, 3691], '91:': [683, 743, 1368, 1551, 1658, 1826, 3696], '479-489Abstract': [684, 744, 1369, 1552, 1659, 1827, 3697], '(6261)': [692, 752, 1377, 1560, 1667, 1835, 3705], 'The': [695, 708, 1120, 1250, 1260, 1407, 1731, 1941, 2388, 2863, 3011, 3032, 3184, 3624, 3735], 'active': [696, 706, 2759, 3417, 3560], 'capase-9': [697], 'then': [698], 'acts': [699], 'an': [701, 761, 1110, 1192, 1329, 1904, 2029, 3845], 'apical': [702], 'generate': [705, 1972, 2316, 2518, 2536, 2758, 3407], 'caspase-3.': [707], 'mediated': [715], 'CARD': [723], 'domain': [724], '(10.Li': [727, 1352, 1535, 1642, 1810, 3680], 'Therefore,': [755, 2159, 2986], 'plays': [760], 'important': [762, 3846], 'role': [763, 3737], 'its': [765, 1321, 2782, 3416, 3482], 'mediation': [768], 'dATP-induced': [772, 3619], 'apoptosis.': [773], 'Ca2+-dependent': [776, 1968, 2073, 3859], '(11.Sorimachi': [780, 801, 898, 2130], 'Ishiura': [782, 803, 900, 2132], 'Suzuki': [784, 805, 902, 2134], 'K.': [785, 806, 903, 2135], '15:': [789, 810, 907, 2139], '721-732Crossref': [790, 811, 908, 2140], '(621)': [792, 813, 910, 2142], 'major': [796], '12.Elce': [816], 'J.S.': [817, 1589, 3787], 'Hegadorn': [818, 1590], 'C.': [819, 1591, 3767], 'Gauthier': [820, 1592], 'Vince': [822, 1594], 'J.W.': [823, 1595], 'Davies': [824, 1596], 'P.L.': [825, 1597], 'Protein': [826, 1598], 'Eng.': [827, 1599], '1995;': [828, 1600], '8:': [829, 1601], '843-848Crossref': [830, 1602], '(65)': [833, 1605], 'Scholar),': [835, 935, 962, 2963], 'μ-calpain': [836], '(calpain': [837, 841], 'I)': [838], 'm-calpain': [840], 'II),': [842], 'distinguished': [845], 'optimal': [848], 'concentration': [850, 1263, 1399, 1938, 2047, 2311, 3582, 3843, 3941, 3965], 'for': [851, 1244, 1257, 1295, 1452, 1489, 1515, 1623, 1789, 1796, 1841, 1850, 2012, 2065, 2171, 2269, 2735, 2781, 3122, 3134, 3145, 3178, 3331, 3558, 3670, 3848, 3989, 3993, 4017, 4043], 'maximal': [852], 'activity.': [853], 'Activation': [854, 3222], 'initiated': [858], 'shows': [862], 'autocleavage': [863], 'large': [866, 1568, 2200, 3206], 'small': [868, 1570, 1853, 2202, 3131], 'subunits.': [869], 'Unlike': [870, 3538], 'require': [873], 'amino': [875, 1883, 2513, 2559], 'acid': [876, 2514, 2560], 'sequences': [877, 2492], 'sites,': [881], 'show': [883, 988, 1012, 2554], 'no': [884, 2386, 2456, 2555, 2976], 'apparent': [885], 'sequence': [886, 2556], 'preferences.': [887], 'It': [888], 'site': [895, 2534, 3449, 3455], 'structure-dependent': [897], 'Several': [913], 'including': [919, 2198], 'p53': [920], '(13.Krbbutat': [921], 'M.H.G.': [922], 'Vousden': [923], 'K.H.': [924], 'Mol.': [925], 'Biol.': [927, 948, 3524, 3721], '17:': [929], '460-468Crossref': [930], '(277)': [933], 'IκBα': [936], '(14.Han': [937], 'Weinman': [939], 'Boldogh': [941], 'Walker': [943], 'R.K.': [944], 'Brasier': [945], 'A.R.': [946], 'Chem.': [949, 3525, 3722], '274:': [951, 3527, 3724], '787-794Abstract': [952], '(219)': [960], 'calpastatin': [964], '(15.Porn-Ares': [965], 'M.I.': [966], 'Samali': [967], 'Cell': [971], 'Death': [972], 'Differ.': [973], '5:': [975, 3793], '1028-1033Crossref': [976], '(185)': [979], 'Even': [982], 'though': [983], 'there': [984], 'evidence': [986], 'apoptosis,': [994, 1903, 3850], 'relationship': [997], 'has': [1003, 2122, 3742], 'not': [1004, 1989, 2258, 2315, 2322, 2575, 2601, 2697, 2757, 2859, 2984, 3231, 3243, 3278, 3312, 3342, 3371, 3406, 3479, 3498, 3604], 'demonstrated.': [1006], 'Using': [1007], 'anin': [1008], 'vitro': [1009, 1331, 1906, 3287], 'assay,': [1010, 1499], 'we': [1011, 2187, 2281, 2626, 2667, 2795, 2964, 3148], 'cytosolic': [1021, 1052, 2239, 2347, 3551, 3592, 3841, 3963], 'factor(s)': [1022], 'Ca2+.': [1027, 1940, 2019, 2086, 2181], 'Analysis': [1028], 'broad': [1031], 'spectrum': [1032], 'protease': [1034, 2169], 'inhibitors': [1035, 1136, 1146, 1994, 2094, 2121, 2149, 2249, 2366, 2384], 'suggests': [1036], 'this': [1038, 2045, 2185, 2255, 2404, 2708, 2923, 3316, 3459], 'factor': [1039], 'calpain.': [1041, 1080], 'Recombinant': [1042], 'II': [1044, 1139, 1511, 1575, 1629, 1776, 2099, 2166, 2195, 2308, 2353, 2803, 2882, 3099, 3119, 3191, 3213, 3225, 3404, 4025], 'similar': [1046, 2232, 2362, 2476, 3167, 3465], 'size': [1047, 2231, 2363, 2471], 'products': [1049, 1945, 2436, 3081], 'factor.': [1053], 'Treatment': [1054], 'ionophore': [1059, 3029, 3897], 'rapid': [1062, 3047, 3903], 'These': [1070, 2002, 2746, 3280, 3484], 'data': [1071, 1107, 2003, 2161, 2747, 2988, 3288, 3485, 3953], 'caspase-9.': [1090, 1621, 2760], 'inhibition': [1099, 1498, 2040, 2105, 2155, 2253, 2977, 3004, 3809, 3828, 3921], 'cytochrome-c-dependent': [1103], 'cleavage.': [1105, 2296, 2545, 2862, 3010, 3127], 'Our': [1106, 3952], 'thus': [1108, 2412, 3596, 3954], 'alternative': [1111], 'way': [1112], 'modulate': [1114], 'signals.': [1119], 'inhibitors,': [1122], 'Z-VAD-fmk,': [1123, 1996], 'Z-DEVD-fmk,': [1124], 'Z-YVAD-fmk': [1126], 'were': [1127, 1140, 1149, 1166, 1185, 1189, 1230, 1277, 1290, 1326, 1410, 1473, 1580, 1632, 1677, 1744, 1782, 1867, 1890, 2302, 2344, 2394, 2446, 3215, 3230, 3430, 3442], 'purchased': [1128], 'Enzyme': [1130], 'Systems': [1131], 'Products': [1132], '(Livermore,': [1133], 'CA).': [1134], 'Calpain': [1135, 2365], 'I': [1137, 2095, 2367, 3136, 3156, 3188, 3210], 'obtained': [1141, 1150], 'Calbiochem.': [1143], 'All': [1144], 'materials': [1148], 'Sigma': [1152], 'unless': [1153], 'otherwise': [1154], 'stated.': [1155], 'For': [1156, 1270, 1497, 1872], 'lysate': [1157, 1306, 1392, 1502, 2176, 2275, 2799, 2824, 3586], 'preparation,': [1158], 'MCF-7': [1159, 1390, 1918, 3275], 'cells,': [1160, 1162, 1579], 'HeLa': [1161, 1500, 2664, 2675, 3271], 'SH-SY5Y': [1164, 1275, 3023, 3327, 3900], 'grown': [1167], 'confluence': [1169, 1281], 'RPMI': [1171], '1640': [1172], "Dulbecco's": [1174], 'modified': [1175], "Eagle's": [1176], 'medium': [1177], '10%': [1179, 1747, 1886], 'fetal': [1180], 'calf': [1181], 'serum,': [1182], 'respectively.': [1183, 4031], 'Cells': [1184], 'harvested': [1186], 'pellets': [1188], 'resuspended': [1190], 'equal': [1193], 'volume': [1194, 1416], 'extraction': [1197], 'buffer': [1198, 1422, 1460, 1705], '(50': [1199], 'mmHEPES-KOH,': [1200], 'pH': [1201, 1426, 1710], '7.5,': [1202, 1427, 1711], '50': [1203, 1387, 1428], 'mm': [1204, 1209, 1213, 1288, 1405, 1424, 1429, 1432, 1435, 1438, 1441, 1445, 1708, 1713, 1716, 1719, 1722, 1725, 1729, 1779], 'KCl,': [1205, 1430], '2': [1206, 1431, 2242, 2443, 2482, 2487, 2582, 2828], 'mmMgCl2,': [1207], '1': [1208, 1212, 1220, 1283, 1287, 1434, 1437, 1440, 1444, 1453, 1490, 1718, 1721, 1724, 1728, 1770, 1961, 2000, 2110], 'EGTA,': [1210, 1436, 1723], 'EDTA)': [1214], 'supplemented': [1215], '5': [1217, 1759, 3052, 3083], 'mmDTT1': [1218], 'mmPMSF.': [1221], 'After': [1222], '30': [1223, 1245, 1418, 1513, 3332], 'min': [1224, 1246, 1517, 3053, 3084, 3333], 'incubation': [1226], 'on': [1227, 1247, 2032, 2077, 2868, 2934, 2970, 3192, 4046], 'ice,': [1228], 'lysed': [1231], 'gently': [1233], 'passing': [1234], '23': [1237], 'G': [1238], 'needle': [1239], 'ten': [1240], 'times': [1241, 1297], 'centrifuged': [1243], 'microcentrifuge.': [1249], 'resultant': [1251], 'supernatant': [1252], '(cell': [1253], 'lysate)': [1254], 'was': [1255, 1264, 1307, 1384, 1461, 1467, 1503, 1611, 1694, 1733, 1764, 1802, 1879, 1909, 1915, 1932, 1946, 1979, 2337, 2703, 2722, 2820, 2825, 2927, 3018, 3057, 3103, 3140, 3176, 3261, 3311, 3355], 'used': [1256, 1617, 1868, 3141], 'biochemical': [1258, 1907, 3914], 'assay.': [1259, 1269], 'total': [1261], 'protein': [1262], 'measured': [1265], 'Bradford': [1268], 'time': [1272, 3033], 'course': [1273, 2585, 3034], 'experiment,': [1274], 'plated': [1278], '75%': [1280], 'overnight.': [1282], 'μm': [1284, 1992], 'A23187': [1285, 3306, 3330], 'CaCl2': [1289], 'added': [1291, 1916], 'culture': [1294], 'various': [1296], 'washed': [1299], 'away': [1300], 'serum-free': [1302], 'medium,': [1303], 'made': [1308, 1411], 'described': [1310, 1347, 1530, 1637, 1805], 'above.': [1311], 'Caspases-7': [1312], '-8': [1314], 'pET15b': [1316], '(Novagen)': [1317, 1325], 'mutants': [1322], 'pET21b': [1324, 1608], 'translated': [1327], 'using': [1328, 2396, 2642, 2879, 3202], 'transcription': [1332], 'translation': [1334], 'kit': [1335], '(Promega)': [1336], 'instruction': [1340], 'manufacturer': [1343], 'purified': [1345, 1696], 'Li': [1349, 1532, 1639, 1807], 'et': [1350, 1533, 1640, 1808], 'al.': [1351, 1534, 1641, 1809], '3': [1380, 1404, 1778, 2717, 2838, 2884, 2908], 'μl': [1381, 1419, 1456], 'of35S-labeled': [1382], 'incubated': [1385, 1448, 1504, 2796], 'μg': [1388, 1760, 1771, 2829], 'final': [1398, 1415], '0.5,': [1401], '1,': [1402], 'CaCl2.': [1406, 1780], 'reaction': [1408, 1465], 'mix': [1409, 1466], 'up': [1412], 'assay': [1421, 1908, 2709], '(20': [1423, 1707, 2096], 'HEPES,': [1425], 'MgCl2,': [1433, 1717], 'EDTA,': [1439, 1720], 'DTT,': [1442, 1726], 'PMSF)': [1446], '37': [1450], '°C': [1451, 1514], 'h.': [1454], '7': [1455], '4×': [1458], 'SDS-loading': [1459], 'added,': [1462], 'subjected': [1468, 1893], '15%': [1470], 'SDS-PAGE.': [1471], 'Proteins': [1472, 1781], 'transferred': [1474, 1783], 'Hybond': [1476, 1785], 'C': [1477, 1786], 'nitrocellulose': [1478, 1787], 'filter': [1479], '(Amersham': [1480], 'Pharmacia': [1481], 'Biotech)': [1482], 'followed': [1483], 'exposure': [1485], 'phosphoimaging': [1487], 'plate': [1488], 'h': [1491], 'visualized': [1493, 1682, 1750], 'phosphoimager.': [1496], 'different': [1506, 1947], 'amounts': [1507, 2220, 2693], 'recombinant': [1509, 1620, 1774, 2192, 2306, 2351, 2397, 2423, 2681, 2801, 4027], '20': [1516, 1991], 'prior': [1518, 2809, 2850], 'addition': [1521, 2277, 2812, 2853], 'Bacteria': [1563], 'strains,': [1564], 'express': [1566, 1619], 'subunits': [1571, 3207], 'rat': [1573, 1773, 2193, 4023], 'same': [1578, 1635, 1737, 2538], 'generous': [1582], 'gift': [1583], 'Dr.': [1585, 4000, 4008], 'John': [1586, 4001, 4041], 'Elce': [1587, 4002], '(12.Elce': [1588], '(C287A)': [1610, 1693, 1763, 2425], 'transformed': [1612], 'BL21': [1614], '(DE3)': [1615], 'Procedures': [1622], 'purification': [1625], 'His-tagged': [1627], 'essentially': [1633], 'Aliquots': [1670, 1739], 'fractions': [1672, 1741], 'Ni2+': [1674], 'column': [1675, 1732], '(Qiagen)': [1676], 'separated': [1678], 'SDS-PAGE': [1680, 1748], 'Coomassie': [1684, 1752], 'Blue': [1685, 1753], 'staining': [1686, 1754], 'determine': [1688], 'positive': [1690, 2932], 'fractions.': [1691], 'Caspase-9': [1692, 2402, 2702], 'further': [1695, 2183, 3019, 3199], 'Superdex': [1698], '200': [1699], 'filtration': [1701], 'chromatography': [1702], 'equilibrated': [1703], 'A': [1706], 'HEPES-KOH,': [1709], '10': [1712], 'KCL,': [1714], '1.5': [1715], 'PMSF).': [1730], 'eluted': [1734], 'buffer.': [1738], '(1': [1742], 'ml)': [1743], 'resolved': [1745], 'Western': [1756, 1790, 1799, 2713, 2890], 'blot': [1757, 1791, 1800, 2714, 2891], 'analysis.': [1758], 'membrane': [1788, 1795, 1878], 'analysis': [1792, 1801, 2715, 2892], 'PVDF': [1794], 'peptide': [1797, 1873, 2491], 'sequencing.': [1798, 1896, 2450, 2467], 'performed': [1803, 2668], 'Dilutions': [1838], '1:2000': [1840, 1849], 'rabbit': [1843], 'anti-caspase-7': [1844], '-9': [1846], 'antibodies': [1847, 1866, 3204], '(PharMingen),': [1848], 'mouse': [1851, 1860], 'anti-calpain': [1852], 'subunit': [1854, 3132], 'antibody': [1855], '(Chemicon),': [1856], '1:5000': [1858], 'anti-rabbit': [1861], 'goat': [1863], 'anti-mouse': [1864], 'secondary': [1865], 'analyses.': [1871], 'sequencing,': [1874], 'polyvinylidene': [1876], 'difluoride': [1877], 'stained': [1880], '0.1%': [1882], 'black': [1884], 'acetic': [1887], 'acid.': [1888], 'Bands': [1889], 'excised': [1891], 'Edman': [1895], 'To': [1897, 2182, 2792], 'identify': [1898], 'factors': [1899, 2240, 2290, 3552, 3593], 'Ca2+-mediated': [1902], 'established': [1910, 2531], 'radiolabeled': [1913], 'lysates': [1920, 2091, 2677], '(Fig.1': [1926, 1986], 'A).': [1927, 3050], 'precursor': [1931, 2899], 'found': [1933], 'increase': [1935, 3937], 'increasing': [1937, 2219, 2692], 'pattern': [1942], 'cytochrome-c-induced': [1951], 'generated': [1954], 'characteristic': [1955, 3409], 'P10': [1956, 2317, 3410], 'P20': [1958, 2319, 3412], 'fragments': [1959, 2320, 3413], '(Fig.': [1960, 1999, 2109, 2481, 2581, 2716, 2837, 2883, 2907, 3048, 3059, 3085, 3112, 3250], 'A,': [1962, 2688, 2718, 3061], 'lane': [1963, 2842, 2888, 3062, 3090, 3252], '2),': [1964], 'suggesting': [1965, 2603, 3116], 'might': [1971], 'caspase-7.': [1975], 'strongly': [1980, 2162, 2749, 3290], 'inhibited': [1981], 'leupeptin': [1983], 'E64': [1985, 2372], 'B)': [1987, 2444], '(DEVD-fmk,': [1995], 'YVAD-fmk': [1998], 'C)).': [2001], 'than': [2008, 3375], 'responsible': [2011, 2170, 2268, 2780, 3121], 'Preincubation': [2020], 'DEVD': [2022], '100': [2024], 'μm,': [2025], 'however,': [2026], 'resulted': [2027, 2102], 'inhibitory': [2030, 2864, 3625, 3736], 'effect': [2031, 2865, 2967, 3626, 3652], 'cleavage,': [2034], 'consistent': [2035, 3283], 'reported': [2038], 'nonspecific': [2039, 2154], 'additional': [2042], 'high': [2046], 'next': [2063], 'tested': [2064, 2188], 'involvement': [2068], 'based': [2076], 'fact': [2079, 2549], 'Indeed': [2087], 'preincubation': [2088], 'μm)': [2097, 2101, 3102], '(5': [2100, 3101], 'full': [2104], 'D,': [2111], 'lanes': [2112, 2486, 2912, 3114], '4': [2113, 3049, 3060], '6).': [2115], 'Although': [2116], 'specificity': [2118, 3169, 3185], 'challenged,': [2124], 'primary': [2126, 2266], 'targets': [2127], 'Higher': [2145], 'concentrations': [2146], 'required': [2151, 3177, 3380, 3557], 'achieve': [2153], 'proteases.': [2158], 'verify': [2184], 'result,': [2186], 'ability': [2190], '(heterodimeric': [2196], 'form': [2197], 'subunits)': [2203], 'vitro.': [2209, 3623], 'As': [2210, 2684], 'Fig.1': [2213], 'E,': [2214], 'Ca2+,': [2222, 2279, 2360], 'cleaves': [2224], 'fragment': [2228, 3466], 'observed': [2235, 2821, 2975, 3263, 3346], 'after': [2236, 2506, 3027, 3054], '(lanes': [2241], '5).': [2244], 'Leupeptin,': [2245], 'E64,': [2246], 'all': [2250], 'showed': [2251, 2385, 2592, 2893, 3038], 'strong': [2252, 2657], '(data': [2257, 2321, 2600, 2983, 3277, 3341, 3370], 'shown).': [2259, 2323, 2985, 3279, 3343, 3372], 'appears': [2262], 'enzyme': [2267], 'upon': [2276], 'although': [2280], 'cannot': [2282, 3149, 3587], 'rule': [2283, 3150], 'out': [2284, 3151], 'possibility': [2286, 2629, 3153], 'cellular': [2289], 'contribute': [2293], 'Short': [2297], '-6': [2301], 'higher': [2310], '(5×)': [2312], 'did': [2314, 2574, 2696, 2858, 3242, 3405, 3478], 'Direct': [2324], 'tested.': [2339], 'Both': [2340], 'proteins': [2348, 2418], '(Fig.2': [2354], 'A)': [2355], 'II,': [2369], 'leupeptin,': [2370], 'blocked': [2373], 'calpain,': [2381], 'whereas': [2382], 'inhibition.': [2387], 'precise': [2389], 'positions': [2391, 2505], 'mapped': [2395], '(Cys-287': [2399], 'Ala).': [2401], 'harboring': [2403], 'mutation': [2405], 'defective': [2407], 'enzymatic': [2409, 2972, 3674], 'activity': [2410, 2655, 2936, 2973, 3675, 3973], 'isolated': [2415], 'full-length': [2417], 'bacteria.': [2420], 'Incubation': [2421, 2844], 'yielded': [2433, 2455, 3420], 'four': [2434], '(C1,': [2437], 'C2,': [2438, 2494], 'C3,': [2439, 2495], 'C4,': [2441], 'Fig.': [2442], 'analyzed': [2447], 'Full-length': [2451], 'C1': [2454], 'information': [2458], 'presumably': [2459, 3562], 'because': [2460, 3232, 3655, 3666], 'modification': [2463], 'blockage': [2465], 'Analyses': [2468], 'C1,': [2473], 'product': [2480, 2539, 2599], 'B,': [2483, 2839, 2885, 2909], 'left': [2484], 'panel,': [2485, 2841, 2887, 2911], '5),': [2489], 'C4': [2497], 'residues': [2507, 2563], '115': [2508, 2516, 2608, 2768], '330.': [2510], 'residue': [2515, 2767], 'would': [2517, 2535, 2634], 'without': [2521, 2774], '(C2).': [2524], 'position': [2527, 2607, 2619, 3460, 3494], '330,': [2528, 2620], 'well': [2530, 3072], '(C1)': [2540], 'Consistent': [2546], 'conservation,': [2557], 'single': [2558], 'mutations': [2561], '330': [2564], '(D→A),': [2565], '287': [2566], '(C→A),': [2567], '315': [2569], '(caspase-9': [2570], 'site,': [2572, 2625], 'D→A)': [2573], 'reduce': [2576], 'C).': [2583], 'Time': [2584], 'experiments': [2586], 'predominant': [2594], 'accumulation': [2595], 'C2': [2598], 'shown),': [2602], 'preferred.': [2610], 'Because': [2611, 2647, 2925, 3128], 'conserved': [2622], 'checked': [2627], 'whether': [2630], 'lead': [2635, 2698, 2997, 3499], 'substrate.': [2646], 'low': [2650], 'level': [2651], 'endogenous': [2653], 'induction': [2658], 'lysates,': [2666], 'adding': [2679], 'exogenous': [2680], 'II.': [2683, 3435], 'Fig.3': [2687], 'monitored': [2711], 'lower': [2719, 2910, 3172], 'panel).': [2720], 'Caspase-3': [2721], 'cytochrome-c,': [2730], 'showing': [2731], 'pathway': [2734, 3757], 'Apaf-1-mediated': [2736], 'subsequent': [2741, 3600, 3978], 'intact.': [2745], 'indicate': [2748], 'does': [2756], 'hypothesized': [2762], 'inactivation': [2783, 2876, 3000, 3979], 'disruption': [2785], 'cytochrome-c-mediated': [2789], 'test': [2793], 'this,': [2794], 'cytochrome-c.': [2816], 'No': [2817], 'when': [2822], 'pre-incubated': [2826], 'upper': [2840, 2886], '7).': [2843], 'alone': [2849], 'reversed': [2873], 'inhibitor': [2881, 3100, 3240], '8).': [2889, 3253], 'reduced': [2895], 'amount': [2896, 3173, 3317], '6and': [2913], '7),': [2914], 'indicating': [2915], 'reaction.': [2924], 'suggested': [2928], 'feedback': [2933], 'examined': [2965], 'these': [2987, 3044], 'indeed': [2996], 'cytochrome-C-induced': [3008], 'demonstratedin': [3020], 'vivo': [3021, 3310], 'human': [3024], 'neuroblastoma': [3025], '(A23187)': [3030], 'treatment.': [3031], 'treatment': [3037, 3898], 'Within': [3051], 'treatment,': [3055], '4).': [3063, 3091], 'correlated': [3070], 'very': [3071, 3313], 'activation,': [3075, 3147], 'appearance': [3078], '4,': [3086, 3113, 3251], 'B': [3087], 'C,': [3089], 'able': [3104], 'block': [3106, 3244], '7)': [3115], 'caspases-7': [3124], '9': [3126], 'autolysis': [3129], '(common': [3133], 'II)': [3139], 'marker': [3144], 'demonstrated': [3166, 3200], 'substrate': [3168], 'will': [3197], 'autolysed': [3219], '(Z-VAD)': [3241], 'Correlation': [3254], 'vivo.': [3299, 3387], 'noticed': [3301], 'cleavagein': [3309], 'efficient.': [3314], 'However,': [3315], 'physiologically': [3322], 'relevant': [3323], 'pre-incubation': [3325], 'protected': [3334], 'etoposide': [3337], 'H7-induced': [3339], 'efficiency': [3349], 'affected': [3356], 'physiological': [3358], 'states': [3359], 'density': [3366], 'differentiation': [3368], 'state': [3369], 'Signals': [3373], 'more': [3384, 3931], 'efficiently': [3385], 'represent': [3415], 'forms,': [3418], 'Upstream': [3423], 'C-terminal': [3446], 'coincides': [3450], '(D330).': [3456], '(C1).': [3472], 'However': [3473], 'result': [3480], 'appropriate': [3493], '(adventitious': [3495], 'proteolysis)': [3496], 'agreement': [3506], 'previous': [3509, 3806], 'observation': [3510, 3801, 3807], '(16.Stennicke': [3511], 'H.R.': [3512, 3709], 'Deveraux': [3513, 3710], 'Q.L.': [3514, 3711], 'Humke': [3515, 3712], 'E.W.': [3516, 3713], 'Reed': [3517, 3714, 3881], 'J.C.': [3518, 3715, 3882], 'Dixit': [3519, 3716], 'V.M.': [3520, 3717], 'Salvesen': [3521, 3718], 'G.S.': [3522, 3719], '8359-8362Abstract': [3528, 3725], '(419)': [3535, 3732], 'proteolysis': [3548], 'precursor,': [3550], '(such': [3553], 'Apaf-1)': [3555], 'binding': [3564], '(in': [3567], 'Apaf-1).': [3578], 'Elevation': [3579, 3839], 'initiation': [3588], 'observed.': [3605], 'demonstrate': [3608, 3893], 'rather': [3630], 'intriguing': [3631], 'it': [3633, 3667], 'represents': [3634], 'novel': [3636], 'mechanism': [3637], 'regulate': [3639], 'elevation': [3643, 3961], 'Ca2+concentration': [3646], 'crucial': [3669], 'self-activation': [3672], 'interacting': [3677], '16.Stennicke': [3708], 'limb-girdle': [3746], 'muscular': [3747], 'dystrophy': [3748], 'type': [3749], '2A': [3750], 'disease': [3751], 'perturbation': [3753], 'IκBα/NF-κB': [3756], '(17.Baghdiguian': [3758], 'Martin': [3760], 'Richard': [3762], 'Pons': [3764], 'F.': [3765, 3874, 3876], 'Astier': [3766], 'Bourg': [3768], 'N.': [3769, 3866], 'Hay': [3770], 'R.T.': [3771], 'Chemaly': [3772], 'Halaby': [3774], 'Loiselet': [3776], 'Anderson': [3778], 'LV.': [3779], 'Munain': [3780], 'A.L.': [3781], 'Fardeau': [3782], 'M': [3783], 'Mangeat': [3784], 'Beckmann': [3786], 'Lefranc': [3788], 'Nature': [3790], 'Med.': [3791], '503-511Crossref': [3794], '(251)': [3797], 'contrary': [3803], 'likely': [3834], 'type-specific.': [3838], 'signal': [3847], 'regulating': [3849], 'dephosphorylation': [3854], 'BAD': [3856], 'calcineurin': [3862], '(18.Wang': [3863], 'H.G.': [3864], 'Pathan': [3865], 'Ethell': [3867], 'I.M.': [3868], 'Krajewski': [3869], 'Yamaguchi': [3871], 'Shibasaki': [3873], 'Mckeon': [3875], 'Bobo': [3877], 'T.': [3878, 3880], 'Franke': [3879], '284:': [3885], '339-343Crossref': [3886], '(967)': [3889], 'preceding': [3910], 'biological': [3912], 'responses': [3915], 'Calpain-dependent': [3920], 'typically': [3932], 'associated': [3933], 'transient': [3936], 'occurs': [3943], 'excitation': [3945], 'muscle': [3950], 'cells.': [3951], 'regulation': [3957], 'part': [3968], 'modulation': [3970], 'thank': [3983, 4034], 'Michael': [3984], 'Chia': [3985], 'Zhihong': [3987], 'Zhou': [3988], 'providing': [3990], 'valuable': [3991], 'reagents': [3992], 'experiments.': [3995], 'grateful': [3998], 'Queens': [4004], 'University': [4005], '(Canada)': 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'created_date': '2016-06-24'}
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