Abstract
This review covers current knowledge on the involvement in apoptosis of a new family of endopeptidases denoted as caspases. Their structure, specific substrates, and inhibitors are considered. The recent classification of cysteine proteases of the caspase family based on their structural and functional features is presented. The biological significance of caspases not related to their proapoptotic effect is discussed.
Similar content being viewed by others
REFERENCES
Fadeel, B., Orrenius, S., and Zhivotovsky, B. (1999) Biochem. Biophys. Res. Commun., 266, 699-717.
Zalessky, V. N., Gavrilenko, T. I., and Philchenkov, A. A. (2002) Lik. Sprava, No. 1, 8-15.
Butenko, Z. A. (1999) Dokl. NAN Ukrainy, No. 1, 185-188.
Philchenkov, A. A., and Stoika, R. S. (1999) Apoptosis and Cancer [in Russian], Morion, Kiev.
Hengartner, M. O. (1999) Recent Progr. Horm. Res., 54, 213-222.
Wu, D., Chen, P. J., Chen, S., Hu, Y., Nunez, G., and Ellis, R. E. (1999) Development, 126, 2021-2031.
Yuan, J., Shaham, S., Ledoux, S., Ellis, H. M., and Horvitz, H. R. (1993) Cell, 76, 641-652.
Zou, H., Henzel, W. J., Liu, X., Lutschg, A., and Wang, X. (1997) Cell, 90, 405-413.
Ahmad, M., Srinivasula, S. M., Hegde, R., Mukattash, R., Fernandes-Alnemri, T., and Alnemri, E. S. (1998) Cancer Res., 58, 5201-5205.
Nicholson, D. W. (1999) Cell Death Differ., 6, 1028-1042.
Zhou, X., Gordon, S. A., Kim, Y. M., Hoffman, R. A., Chen, Y., Zhang, X. R., Simmons, R. L., and Ford, H. R. (2000) J. Immunol., 165, 1252-1258.
Krippner-Heidenreich, A., Talanian, R. V., Sekul, R., Kraft, R., Thole, H., Ottleben, H., and Luscher, B. (2001) Biochem. J., 358, 705-715.
Kutsyi, M. P., Kuznetsova, E. A., and Gaziev, A. I. (1999) Biochemistry (Moscow), 64, 115-126.
Wolf, B. B., and Green, D. R. (1999) J. Biol. Chem., 274, 20049-20052.
Shi, Y. (2002) Mol. Cell, 9, 459-470.
Riedl, S. J., Fuentes-Prior, P., Renatus, M., Kairies, N., Krapp, S., Huber, R., Salvesen, G. S., and Bode, W. (2001) Proc. Natl. Acad. Sci. USA, 98, 14790-14795.
Srinivasula, S. M., Ahmad, M., Fernandes-Alnemri, T., and Alnemri, E. S. (1998) Mol. Cell., 1, 949-957.
Muzio, M., Stockwell, B. R., Stennicke, H. R., Salvesen, G. S., and Dixit, V. M. (1998) J. Biol. Chem., 273, 2926-2930.
Duan, H., and Dixit, V. (1997) Nature, 385, 86-89.
Thome, M., Hofmann, K., Burns, K., Martinon, F., Bodmer, J. L., Mattmann, C., and Tschopp, J. (1998) Curr. Biol., 8, 885-888.
Hlaing, T., Guo, R. F., Dilley, K. A., Loussia, J. M., Morrish, T. A., Shi, M. M., Vincenz, C., and Ward, P. A. (2001) J. Biol. Chem., 276, 9230-9238.
Razmara, M., Srinivasula, S. M., Wang, L., Poyet, J. L., Geddes, B. J., DiStefano, P. S., Bertin, J., and Alnemri, E. S. (2002) J. Biol. Chem., 277, 13952-13958.
Poyet, J. L., Srinivasula, S. M., Tnani, M., Razmara, M., Fernandes-Alnemri, T., and Alnemri, E. S. (2001) J. Biol. Chem., 276, 28309-28313.
Inohara, N., Koseki, T., del Peso, L., Hu, Y., Yee, C., Chen, S., Carrio, R., Merino, J., Liu, D., Ni, J., and Nunez, G. (1999) J. Biol. Chem., 274, 14560-14567.
Zheng, L., Schickling, O., Peter, M. E., and Lenardo, M. J. (2001) J. Biol. Chem., 276, 31945-31952.
Hofmann, K. (1999) Cell. Mol. Life Sci., 55, 1113-1128.
Butt, A. J., Harvey, N. L., Parasivam, G., and Kumar, S. (1998) J. Biol. Chem., 273, 6763-6768.
Renatus, M., Stennicke, H. R., Scott, F. L., Liddington, R. C., and Salvesen, G. S. (2001) Proc. Natl. Acad. Sci. USA, 98, 14250-14255.
Slee, E. A., Harte, M. T., Kluck, R. M., Wolf, B. B., Casiano, C. A., Newmeyer, D. D., Wang, H. G., Reed, J. C., Nicholson, D. W., Alnemri, E. S., Green, D. R., and Martin, S. J. (1999) J. Cell. Biol., 144, 281-292.
Ruiz-Vela, A., Gonzalez de Buitrago, G., and Martinez, A. C. (1999) EMBO J., 18, 4988-4998.
Zhou, Q., and Salvesen, G. S. (1997) Biochem. J., 324, 361-364.
Vancompernolle, K., van Herreweghe, F., Pynaert, G., van de Craen, M., de Vos, K., Totty, N., Sterling, A., Fiers, W., Vandenabeele, P., and Grooten, J. (1998) FEBS Lett., 438, 150-158.
Van de Craen, M., Declercq, W., van den Brande, I., Fiers, W., and Vandenabeele, P. (1999) Cell Death Differ., 6, 1117-1124.
Kang, S. J., Wang, S., Hara, H., Peterson, E. P., Namura, S., Amin-Hanjani, S., Huang, Z., Srinivasan, A., Tomaselli, K. J., Thornberry, N. A., Moskowitz, M. A., and Yuan, J. (2000) J. Cell Biol., 149, 613-622.
Guo, Y., Srinivasula, S. M., Druilhe, A., Fernandes-Alnemri, T., and Alnemri, E. S. (2002) J. Biol. Chem., 277, 13430-13437.
Thornberry, N. A., Rano, T. A., Peterson, E. P., Rasper, D. M., Timkey, T., Garcia-Calvo, M., Houtzager, V. M., Nordstrom, P. A., Roy, S., Vaillancourt, J. P., Chapman, K. T., and Nicholson, D. W. (1997) J. Biol. Chem., 272, 17907-17911.
Thornberry, N. A., and Lazebnik, Y. (1998) Science, 281, 1312-1316.
Widmann, C., Gibson, S., and Johnson, G. L. (1998) J. Biol. Chem., 273, 7141-7147.
Rao, L., Perez, D., and White, E. (1996) J. Cell Biol., 135, 1441-1455.
Hirata, H., Takahashi, A., Kobayashi, S., Yonehara, S., Sawai, H., Okazaki, T., Yamamoto, K., and Sasada, M. (1998) J. Exp. Med., 187, 587-600.
Sahara, S., Aoto, M., Eguchi, Y., Imamoto, N., Yoneda, Y., and Tsujimoto, Y. (1999) Nature, 401, 168-173.
Enari, M., Sakahira, H., Yokoyama, H., Okawa, K., Iwamatsu, A., and Nagata, S. (1998) Nature, 391, 43-50.
Ekert, P. G., Silke, J., and Vaux, D. L. (1999) Cell Death Differ., 6, 1081-1086.
Komiyama, T., Quan, L. T., and Salvesen, G. S. (1996) Adv. Exp. Med. Biol., 389, 173-176.
Okuyama, T., Kosuga, M., and Li, X. (1999) Hum. Cell, 12, 125-130.
Hershberger, P. A., Dickson, J. A., and Friesen, P. D. (1992) J. Virol., 66, 5525-5533.
Zhou, Q., Krebs, J. F., Snipas, S. J., Price, A., Alnemri, E. S., Tomaselli, K. J., and Salvesen, G. S. (1998) Biochemistry, 37, 10757-10765.
Verhagen, A. M., Coulson, E. J., and Vaux, D. L. (2001) Genome Biol., 2, 3009-1_3009.10.
Richter, B. W., Mir, S. S., Eiben, L. J., Lewis, J., Reffey, S. B., Frattini, A., Tian, L., Frank, S., Youle, R. J., Nelson, D. L., Notarangelo, L. D., Vezzoni, P., Fearnhead, H. O., and Duckett, C. S. (2001) Mol. Cell. Biol., 21, 4292-4301.
Roy, N., Deveraux, Q. L., Takahashi, R., Salvesen, G. S., and Reed, J. C. (1997) EMBO J., 16, 6914-6925.
Takahashi, R., Deveraux, Q., Tamm, I., Welsh, K., Assa-Munt, N., Salvesen, G. S., and Reed, J. C. (1998) J. Biol. Chem., 273, 7787-7790.
McCarthy, J. V., Ni, J., and Dixit, V. M. (1998) J. Biol. Chem., 273, 16968-16975.
Goyal, L. (2001) Cell, 104, 805-808.
Li, F., Ambrosini, G., Chu, E. Y., Plescia, J., Tognin, S., Marchisio, P. C., and Altieri, D. C. (1998) Nature, 396, 580-584.
Tamm, I., Wang, Y., Sausville, E., Scudiero, D. A., Vigna, N., Oltersdorf, T., and Reed, J. C. (1998) Cancer Res., 58, 5315-5320.
Shin, S., Sung, B. J., Cho, Y. S., Kim, H. J., Ha, N. C., Hwang, J. I., Chung, C. W., Jung, Y. K., and Oh, B. H. (2001) Biochemistry, 40, 1117-1123.
Kasof, G. M., and Gomes, B. C. (2001) J. Biol. Chem., 276, 3238-3246.
Wu, G., Chai, J., Suber, T. L., Wu, J. W., Du, C., Wang, X., and Shi, Y. (2000) Nature, 408, 1008-1012.
Martins, L. M., Iaccarino, I., Tenev, T., Gschmeissner, S., Totty, N. F., Lemoine, N. R., Savopoulos, J., Gray, C. W., Creasy, C. L., Dingwall, C., and Downward, J. (2002) J. Biol. Chem., 277, 439-444.
Verhagen, A. M., Ekert, P. G., Pakusch, M., Silke, J., Connolly, L. M., Reid, G. E., Moritz, R. L., Simpson, R. J., and Vaux D. L. (2000) Cell, 102, 43-53.
Irmler, M., Thome, M., Hahne, M., Schneider, P., Hofmann, K., Steiner, V., Bodmer, J. L., Schroter, M., Burns, K., Mattmann, C., Rimoldi, D., French, L. E., and Tschopp, J. (1997) Nature, 388, 190-195.
Scaffidi, C., Schmitz, I., Krammer, P. H., and Peter, M. E. (1999) J. Biol. Chem., 274, 1541-1548.
Philchenkov, A. A., and Butenko, Z. A. (2000) Biopolim. Kletka, 16, 122-135.
Zhang, H., Xu, Q., Krajewski, S., Krajewska, M., Xie, Z., Fuess, S., Kitada, S., Godzik, A., and Reed, J. C. (2000) Proc. Natl. Acad. Sci. USA, 97, 2597-2602.
Koseki, T., Inohara, N., Chen, S., and Nunez, G. (1998) Proc. Natl. Acad. Sci. USA, 95, 5156-5160.
Schendel, S. L., Montal, M., and Reed, J. C. (1998) Cell Death Differ., 5, 372-380.
Saito, M., Korsmeyer, S. J., and Schlesinger, P. H. (2000) Nat. Cell Biol., 2, 553-555.
Narita, M., Shimizu, S., Ito, T., Chittenden, T., Lutz, R. J., Matsuda, H., and Tsujimoto, Y. (1998) Proc. Natl. Acad. Sci. USA, 95, 14681-14686.
Shimizu, S., Narita, M., and Tsujimoto, Y. (1999) Nature, 399, 483-487.
Okuno, S., Shimizu, S., Ito, T., Nomura, M., Hamada, E., Tsujimoto, Y., and Matsuda, H. (1998) J. Biol. Chem., 273, 34272-34277.
Rudel, T. (1999) Herz, 24, 236-241.
Schotte, P., Declercq, W., van Huffel, S., Vandenabeele, P., and Beyaert, R. (1999) FEBS Lett., 442, 117-121.
Alexandre, S., Rast, C., Nguyen-Ba, G., and Vasseur, P. (2000) Exp. Cell Res., 255, 30-39.
Zhivotovsky, B., Samali, A., Gahm, A., and Orrenius, S. (1999) Cell Death Differ., 6, 644-651.
Shikama, Y. U. M., Miyashita, T., and Yamada, M. (2001) Exp. Cell Res., 264, 315-325.
Mancini, M., Machamer, C. E., Roy, S., Nicholson, D. W., Thornberry, N. A., Casciola-Rosen, L. A., and Rosen, A. (2000) J. Cell Biol., 149, 603-612.
Chandler, J. M., Cohen, G. M., and MacFarlane, M. (1998) J. Biol. Chem., 273, 10815-10818.
Nakagawa, T., Zhu, H., Morishima, N., Li, E., Xu, J., Yankner, B. A., and Yuan, J. (2000) Nature, 403, 98-103.
Mao, P. L., Jiang, Y., Wee, B. Y., and Porter, A. G. (1998) J. Biol. Chem., 273, 23621-23624.
Singh, A. B., Kaushal, V., Megyesi, J. K., Shah, S. V., and Kaushal, G. P. (2002) Kidney Int., 62, 106-115.
Rao, R. V., Hermel, E., Castro-Obregon, S., del Rio, G., Ellerby, L. M., Ellerby, H. M., and Bredesen, D. E. (2001) J. Biol. Chem., 276, 33869-33874.
Morishima, N., Nakanishi, K., Takenouchi, H., Shibata, T., and Yasuhiko, Y. (2002) J. Biol. Chem., 277, 34287-34294.
Flavell, R. A., Kuida, K., Zheng, T. S., Haydar, T. F., Kuan, C. Y., Su, M. S., and Rakic, P. (2000) in Apoptosis in Health and Disease (Ruffolo, R. R., and Walsh, F., eds.) Harwood Academic Publishers, Amsterdam, pp. 47-60.
Zheng, T. S., Hunot, S., Kuida, K., Momoi, T., Srinivasan, A., Nicholson, D. W., Lazebnik, Y., and Flavell, R. A. (2000) Nat. Med., 6, 1241-1247.
Dinarello, C. A. (1999) J. Allergy Clin. Immunol., 103, 11-24.
Los, M., Wesselborg, S., and Schulze-Osthoff, K. (1999) Immunity, 10, 629-639.
Li, P., Allen, H., Banerjee, S., and Seshadri, T. (1997) J. Cell Biochem., 64, 27-32.
Zheng, T. S., Hunot, S., Kuida, K., and Flavell, R. A. (1999) Cell Death Differ., 6, 1043-1053.
Zhang, Y., Center, D. M., Wu, D. M., Cruikshank, W. W., Yuan, J., Andrews, D. W., and Kornfeld, H. (1998) J. Biol. Chem., 273, 1144-1149.
Ludwiczek, O., Kaser, A., Koch, R. O., Vogel, W., Cruikshank, W. W., and Tilg, H. (2001) Eur. Cytokine Netw., 12, 478-486.
Posmantur, R., Wang, K. K., and Gilbertsen, R. B. (1998) Exp. Cell Res., 244, 302-309.
Philchenkov, A. A., Stepanov, Yu. M., Lipkin, V. M., and Kushlinsky, N. E. (2002) Allergol. Immunol. (Moscow), 3, 24-35.
Kim, S. O., and Han, J. (2001) J. Endotoxin Res., 7, 292-296.
Rincheval, V., Renaud, F., Lemaire, C., Mignotte, B., and Vayssiere, J. L. (1999) FEBS Lett., 460, 203-206.
Droin, N., Beauchemin, M., Solary, E., and Bertrand, R. (2000) Cancer Res., 60, 7039-7047.
Huang, Y., Shin, N. H., Sun, Y., and Wang, K. K. (2001) Biochem. Biophys. Res. Commun., 283, 762-769.
Angelastro, J. M., Moon, N. Y., Liu, D. X., Yang, A. S., Greene, L. A., and Franke, T. F. (2001) J. Biol. Chem., 276, 12190-12200.
Kudryavetz, Yu. I., Philchenkov, A. A., Slukvin, I. I., Abramenko, I. V., and Belous, N. I. (1996) Med. Biol. Environ., 24, 71-79.
Goebel, S., Gross, U., and Lüder, C. G. K. (2001) J. Cell Sci., 114, 3495-3505.
Stephano, A., Scarabelli, T. M., Knight, R. A., and Latchman, D. S. (2002) J. Biol. Chem., 277, 13693-13699.
Miossec, C., Dutilleul, V., Fassy, F., and Diu-Hercend, A. (1997) J. Biol. Chem., 272, 13459-13462.
Wilhelm, S., Wagner, H., and Hacker, G. (1998) Eur. J. Immunol., 28, 891-900.
Alam, A., Cohen, L. Y., Aouad, S., and Sekaly, R. P. (1999) J. Exp. Med., 190, 1879-1890.
Kennedy, N. J., Kataoka, T., Tschopp, J., and Budd, R. C. (1999) J. Exp. Med., 190, 1891-1896.
Ramadani, M., Yang, Y., Gansauge, F., Gansauge, S., and Beger, H. G. (2001) Pancreas, 22, 383-387.
Frost, V., Al-Mehairi, S., and Sinclair, A. J. (2001) Oncogene, 20, 2737-2748.
Levkau, B., Koyama, H., Raines, E. W., Clurman, B. E., Herren, B., Orth, K., Roberts, J. M., and Ross, R. (1998) Mol. Cell, 1, 553-563.
Pandey, P., Nakazawa, A., Ito, Y., Datta, R., Kharbanda, S., and Kufe, D. (2000) Oncogene, 19, 3941-3947.
Doyle, B. T., O'Neill, A. J., Newsholme, P., Fitzpatrick, J. M., and Watson, R. W. (2002) J. Leukocyte Biol., 71, 247-254.
Ito, Y., Pandey, P., Sporn, M. B., Datta, R., Kharbanda, S., and Kufe, D. (2001) Mol. Pharmacol., 59, 1094-1099.
Di Bacco, A. M., and Cotter, T. G. (2002) Br. J. Haematol., 117, 588-597.
Zermati, Y., Garrido, C., Amsellem, S., Fishelson, S., Bouscary, D., Valensi, F., Varet, B., Solary, E., and Hermine, O. (2001) J. Exp. Med., 193, 247-254.
Dahm, R. (1999) Ophthalmic Res., 31, 163-183.
Weil, M., Raff, M. C., and Braga, V. M. (1999) Curr. Biol., 9, 361-364.
Lippens, S., Kockx, M., Knaapen, M., Mortier, L., Polakowska, R., Verheyen, A., Garmyn, M., Zwijsen, A., Formstecher, P., Huylebroeck, D., Vandenabeele, P., and Declercq, W. (2000) Cell Death Differ., 7, 1218-1224.
Watanabe, Y., and Akaike, T. (1999) J. Cell. Physiol., 179, 45-51.
Levkau, B., Herren, B., Koyama, H., Ross, R., and Raines, E. W. (1998) J. Exp. Med., 187, 579-586.
Antonopoulos, C., Cumberbatch, M., Dearman, R. J., Daniel, R. J., Kimber, I., and Groves, R. W. (2001) J. Immunol., 166, 3672-3677.
Wang, B., Feliciani, C., Howell, B. G., Freed, I., Cai, Q., Watanabe, H., and Sauder, D. N. (2002) J. Immunol., 168, 3303-3308.
Lamkanfi, M., Declercq, W., Kalai, M., Saelens, X., and Vandenabeele, P. (2002) Cell Death Differ., 9, 358-361.
Madeo, F., Herker, E., Maldener, C., Wissing, S., Lächelt, S., Herlan, M., Fehr, M., Lauber, K., Sigrist, S. J., Wesselborg, S., and Fröhlich, K.-U. (2002) Mol. Cell, 9, 911-917.
Uren, A. G., O'Rourke, K., Aravind, L. A., Pisabarro, M. T., Seshagiri, S., Koonin, E. V., and Dixit, V. M. (2000) Mol. Cell, 6, 961-967.
Seery, J. P., Cattell, V., and Watt, F. M. (2001) J. Immunol., 167, 2452-2455.
Nuttall, M. E., Lee, D., McLaughlin, B., and Erhardt, J. A. (2001) Drug Discov. Today, 6, 85-91.
Zalessky, V. N., and Philchenkov, A. A. (2001) Sovr. Probl. Toksikol., No. 4, 64-70.
Concha, N. O., and Abdel-Meguid, S. S. (2002) Curr. Med. Chem., 9, 713-726.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Philchenkov, A.A. Caspases as Regulators of Apoptosis and Other Cell Functions. Biochemistry (Moscow) 68, 365–376 (2003). https://doi.org/10.1023/A:1023635510363
Issue Date:
DOI: https://doi.org/10.1023/A:1023635510363