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Cross-talk between Two Cysteine Protease Families: Activation of Caspase-12 by Calpain in Apoptosis

Correspondence to: Junying Yuan, Department of Cell Biology, Harvard Medical School, 240 Longwood Ave., Boston, MA 02115. Tel:(617) 432-4170 Fax:(617) 432-4177 E-mail:jyuan{at}hms.harvard.edu.

Calpains and caspases are two cysteine protease families that play important roles in regulating pathological cell death. Here, we report that m-calpain may be responsible for cleaving procaspase-12, a caspase localized in the ER, to generate active caspase-12. In addition, calpain may be responsible for cleaving the loop region in Bcl-xL and, therefore, turning an antiapoptotic molecule into a proapoptotic molecule. We propose that disturbance to intracellular calcium storage as a result of ischemic injury or amyloid ß peptide cytotoxicity may induce apoptosis through calpain- mediated caspase-12 activation and Bcl-xL inactivation. These data suggest a novel apoptotic pathway involving calcium-mediated calpain activation and cross-talks between calpain and caspase families.

Key Words: calcium, Alzheimer's disease, Bcl-xL, endoplasmic reticulum, ER stress

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• CADET, J. L., JAYANTHI, S., DENG, X. (2003). Speed kills: cellular and molecular bases of methamphetamine-induced nerve terminal degeneration and neuronal apoptosis. FASEB J. 17: 1775-1788 [Abstract] [Full Text]  
• Luo, S., Baumeister, P., Yang, S., Abcouwer, S. F., Lee, A. S. (2003). Induction of Grp78/BiP by Translational Block: ACTIVATION OF THE Grp78 PROMOTER BY ATF4 THROUGH AN UPSTREAM ATF/CRE SITE INDEPENDENT OF THE ENDOPLASMIC RETICULUM STRESS ELEMENTS. J. Biol. Chem. 278: 37375-37385 [Abstract] [Full Text]  
• Reimertz, C., Kogel, D., Rami, A., Chittenden, T., Prehn, J. H.M. (2003). Gene expression during ER stress-induced apoptosis in neurons: induction of the BH3-only protein Bbc3/PUMA and activation of the mitochondrial apoptosis pathway. JCB 162: 587-597 [Abstract] [Full Text]  
• DeBiasi, R. L., Clarke, P., Meintzer, S., Jotte, R., Kleinschmidt-Demasters, B. K., Johnson, G. L., Tyler, K. L. (2003). Reovirus-Induced Alteration in Expression of Apoptosis and DNA Repair Genes with Potential Roles in Viral Pathogenesis. J. Virol. 77: 8934-8947 [Abstract] [Full Text]  
• Kalai, M., Lamkanfi, M., Denecker, G., Boogmans, M., Lippens, S., Meeus, A., Declercq, W., Vandenabeele, P. (2003). Regulation of the expression and processing of caspase-12. JCB 162: 457-467 [Abstract] [Full Text]  
• Zong, W.-X., Li, C., Hatzivassiliou, G., Lindsten, T., Yu, Q.-C., Yuan, J., Thompson, C. B. (2003). Bax and Bak can localize to the endoplasmic reticulum to initiate apoptosis. JCB 162: 59-69 [Abstract] [Full Text]  
• GOLL, D. E., THOMPSON, V. F., LI, H., WEI, W., CONG, J. (2003). The Calpain System. Physiol. Rev. 83: 731-801 [Abstract] [Full Text]  

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