Bcl-2 family proteins

Adams JM. The Bcl-2 protein family arbiters of cell survival. Science 1998 281 1322-1326. 

Y. Saintigny, A. Dumay, S. Lambert and B. S. Lopez, A novel role for the Bcl-2 protein family specific suppression of the RAD51 recombination pathway, Embo /., 2001, 20(10), 2596. 

Adams, J.M. and Cory, S. The BCl-2 protein family Arbiters of cell survival (1998) Science 281,... 

Altznauer, F., Conus, S., Cavalli, A., Folkers, G. and Simon, H. U., 2004, Calpain-1 regulates Bax and subsequent Smac-dependent caspase-3 activation in neutrophil apoptosis. J Biol Chem 279, 5947-57. Antonsson, B. and Martinou, J. C., 2000, The Bcl-2 protein family. Exp Cell Res 256, 50-7. Benali-Furet, N. L., Chami, M., Houel, L., De Giorgi, F., Vernejoul, F., Lagorce, D., Buscail, L., Bartenschlager, R., Ichas, F., Rizzuto, R. and Paterlini-Brechot, P., 2005, Hepatitis C virus core... 

L-Digitoxose (53L) and its 4-(9-acetyl derivative are present in a tetrasaccha-ride glycosidically linked in tetrocarcin A, an antibiotic inhibitor of the anti-poptotic Bcl-2 protein family.123 Other tetrocarcins have been isolated from the culture of Micromonospora chalcea KY 11091.124 From another strain of Micromonospora, analogues of tetrocarcin A, called arisostatins A and B, containing isobutanoyldigitoxose instead of acetyldigitoxose were isolated.125... 

Members of the Bcl-2 protein family are key regulators of the mitochondrial step in apoptotic pathway (44). Upregulation of antiapoptotic Bcl-2 family members is commonly observed in many types of cancers and is well established to play a major... 

Youle RJ, Strasser A. The BCL-2 protein family opposing 65. activities that mediate cell death. Nat. Rev. Mol. Cell Biol. 2008 9 47-59. 

It was first observed in type Type 2 B-cell lymphoma that the translocation of the Bcl-2 gene leads to radical overexpression of Bcl-2 (10). The overproduction of Bcl-2 has been shown to be transforming (10). Members of the Bcl-2 protein family contain as many as four characteristically helical Bcl-2 homology motifs (BH1-BH4). Bcl-2 proteins are divided into classes, as prosurvival proteins (Bcl-2, Bc1-xl, Mc1-1, A-1, and Bcl-w), proapoptotic proteins (Bak and Bax), and proapoptotic proteins that contain only the BH3 motif (Bim, Bid, Puma, and Noxa) (3, 11). The manner in which the different Bcl-2 family members interact and the mechanisms by which cytochrome c release is initiated are unclear, but the central role of the Bcl-2 family in apoptosis, and the therapeutic potential of regulating these proteins, is well established. 

Krajewski, S., Krajewski, M., and Reed, J. C. (1996) Immunohistochemical analysis of in vivo patterns of Bak expression, a proapoptotic member of the Bcl-2 protein family. Cancer Res. 56,2849-2855. 

Borner, C. The Bcl-2 protein family sensors and checkpoints for life-or-death decisions. Mol. Immunol. 39 615-647, 2003. 

Bcl-2 protein family A family of genes and proteins that either protect against (Bcl-2 proper, Bcl-xL, Bcl-w) or initiate (Bax, BAD, Bak, and Bok) apoptosis by governing the mitochondrial outer membrane permeabilization. 

Jerry M. Adams and Suzanne Cory. The bcl-2 protein family Arbiters of cell survival. Science, 281(5381) 1322-1326, 1998. 

Figure 18.6 The mammalian Bcl-2 protein family. The distinct BH domains are shown for each representative member of the family. In addition, heterodimerization regions are indicated.

M. Adams, S. Cory, The Bcl-2 protein family arbiters of cell survival, Science 1998, 281, 1322-1326 J.C. Reed, Double identity for proteins of the Bcl-2 family, Nature 1997, 387, 773-776. 

L.H., Thompson, C.B., Golemis, E., Fong, L., Wang, H.G. et al. (1994) Interactions among members of the Bcl-2 protein family analyzed with a yeast two-hybrid system. Proc. Natl. Acad. Sci. USA9 9238-9242. 

Adams, J.M. Cory, S. (1998) Science, 281, 1322-1326. The Bcl-2 Protein Family Arbiters of Cell Survival. 

Figure 3 The role of MARK signaling pathways in mitochondria-dependent apoptosis antioxidant enzymes, the Bcl-2 protein family, and the influence of flavonoids and isoflavonoids. MARK, mitogen-activated protein kinase.

Activated MAPKs have been found to modulate mitochondria-mediated apoptotic pathways, JNK in particular [71]. In fact, it appears that MAPK signaling may represent a potential cross-link between die different apoptotic pathways. JNK activation is not required for death-receptor-mediated apoptosis but is required for caspase-9 activation by the mitochondrial pathway, induced by a variety of proapoptotic stimuli [72,73]. JNK activation and c-Jun phosphorylation were found to be necessary to promote cytochrome c release from mitochondria, with the sequential assembly of the apoptosome and caspase-3 activation. The molecular mechanism of this effect was unclear, but it appeared to involve regulation of the expression and phosphorylation state of the Bcl-2 protein family and their recruitment to the mitochondrial outer membrane (Fig. 4). In a number of apoptotic models, JNK activation was associated with a downregulation of the antiapoptotic Bcl-2 and Bc1-Xl and upregulation of the proapoptotic Bax and Bad [74—77]. Two cell culture studies provided very strong evidence that JNK activation resulted in the phosphorylation of Bcl-2 and Bc1-Xl ex vivo, with the induction of apoptosis [76,77]. In other words, Bcl-2 and Bc1-Xl appear to be substrates of JNK, and phosphorylation results in their inactivation, thereby abolishing their ability to prevent cytochrome c release. 

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