Apoptosis proteins

Active caspases 8, 9 and 10 can convert caspase-3, the most abundant effector caspase from its pro-form to its active cleaved form. Cleavage of a number of different substrates by caspase-3 and also by caspase-6 and -7 which are two other executioner caspases besides caspase-3 then results in the typical morphology which is characteristic of apoptosis. Yet, the activation of caspase-3 and also of caspase-9 can be counteracted by IAPs, so called inhibitor of apoptosis proteins. However, concomitantly with cytochrome C also other proteins are released from mitochondria, including Smac/DIABLO. Smac/DIABLO and potentially other factors can interact with IAPs and thereby neutralize their caspase-inhibitory activity. This releases the breaks on the cell death program and allows apoptosis to ensue. 

Eckelman BP, Salvesen G, Scott FL (2006) Human inhibitor of apoptosis proteins why XIAP is the black sheep of the family. EMBO Rep 7 988-994... 

Negative regulation of apoptosis is effected by inhibitor of apoptosis proteins. Another means of controling apoptosis is by altering the stabilization of mitochondria, which is largely determined by the interplay between the pro- and antiapoptotic members of the Bcl2 family [4]. 

HBV, hepatitis B HCV, hepatitis C IAP, inhibitor of apoptosis protein DBM, IAP binding motifs INCA, inhibitory CARD NASH, non-alcoholic steatohepatitis PCD, programmed cell death PCI, pan-caspase inhibitor OA, osteoarthritis RA, rheumatoid arthritis Smac, second mitochondria-derived activator of caspases TRAIL, tumor necrosis factor-related apoptosis-inducing ligand. 

Fulda S (2007) Inhibitor of apoptosis proteins as targets for anticancer therapy. Expert Rev Anticancer Ther 7 1255-1264... 

Tun C, Guo W, Nguyen H, Yun B, Libby RT, Morrison RS, Garden GA (2007) Activation of the extrinsic caspase pathway in cultured cortical neurons requires p53-mediated down-regulation of the X-linked inhibitor of apoptosis protein to induce apoptosis. J Neurochem 102 1206-1219... 

G. M. Rubin, Drosophila homologs of baculovirus inhibitor of apoptosis proteins function to block cell death. Cell, 1995, 83(7), 1253-62. 

Vucic, D., W. J. Kaiser, and L. K. Miller, Inhibitor of apoptosis proteins physically interact with and block apoptosis induced by Drosophila proteins HID and GRIM. Mol Cell Biol, 1998, 18(6), 3300-9. 

Suzuki, Y., Y. Nakabayashi, and R. Takahashi, Ubiquitin-protein ligase activity of X-linked inhibitor of apoptosis protein promotes protea-... 

Rothe, M., et al.. The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins. Cell,... 

Nachmias, B., Ashhab, Y., Ben-Yehuda, D. (2004) The inhibitor of apoptosis protein family (IAPs) an emerging therapeutic target in cancer. Semin Cancer Biol 14, 231-243. 

Kim G. M., Xu J., Xu J. M., Song S. K., Yan P., Ku G., Xu X. M., and Hsu C. Y. (2001). Tumor necrosis factor receptor deletion reduces nuclear factor-kappa B activation, cellular inhibitor of apoptosis protein 2 expression, and functional recovery after traumatic spinal cord injury. J. Neurosci. 21 6617-6625. 

Granda, T.G., Iiu, X.H., Smaaland, R., Cermakian, N., Filipski, E., Sassone-Corsi, P., Levi, F. Circadian regulation of cell cycle and apoptosis proteins in mouse bone marrow and tumor. FASEB J. 2005, 19 304-306. 

IAP Inhibitor of apoptosis proteins XIAP, APB, ILP, HILP, HIAP2,... 

Rothe, M., Pan, M. G., Henzel, W. J., Ayres, T. M., and Goeddel, D. V. (1995). The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins. Cell 83, 1243-1252. 

Natural Inhibitors of the Inhibitor of Apoptosis Proteins lAP Antagonists. . 31... 

Caspases kill cells by cleaving abroad spectrum of cellular substrates. To ensure that the death pathway is not accidentally activated, caspase activity must be carefully regulated to prevent aberrant caspase activation. Some members of the inhibitor of apoptosis protein (lAP) family can suppress caspase activity thus avoiding unwanted... 

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