Sandbox Reserved 1122: Difference between revisions
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On the other hand, Bcl-2 may prevent the activation and homo-oligomerization of Bax and Bak thus blocking the cell death. This is achieved by sequestering BH3-only proteins or activated and monomeric Bax and Bak. <scene name='71/719863/Scenebh1/1'>BH1</scene> and <scene name='71/719863/Scenebh2/1'>BH2</scene> are essential for Bcl-2/Bax heterodimer formation. The conservation of each amino acid seems to be very important to this interaction. <ref>[http://www.nature.com.scd-rproxy.u-strasbg.fr/nature/journal/v369/n6478/pdf/369321a0.pdf BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax] </ref><ref>[http://jcs.biologists.org/content/122/4/437 Control of mitochondrial apoptosis by the Bcl-2 family] </ref> | On the other hand, Bcl-2 may prevent the activation and homo-oligomerization of Bax and Bak thus blocking the cell death. This is achieved by sequestering BH3-only proteins or activated and monomeric Bax and Bak. <scene name='71/719863/Scenebh1/1'>BH1</scene> and <scene name='71/719863/Scenebh2/1'>BH2</scene> are essential for Bcl-2/Bax heterodimer formation. The conservation of each amino acid seems to be very important to this interaction. <ref>[http://www.nature.com.scd-rproxy.u-strasbg.fr/nature/journal/v369/n6478/pdf/369321a0.pdf BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax] </ref><ref>[http://jcs.biologists.org/content/122/4/437 Control of mitochondrial apoptosis by the Bcl-2 family] </ref> | ||
Therefore, the neutralization of Bcl-2 is required for eficient cell-death. BH3 proteins Bad, Bim and Puma bind Bcl-2 and disable its anti-apoptotic activity. BH3 peptides occupy the hydrophobic pocket of Bcl-2 and the sequestered pro-apoptotic proteins are released. <ref>[http://www.cell.com/molecular-cell/fulltext/S1097-2765(05)01040-3 Differential Targeting of Prosurvival Bcl-2 Proteins by Their BH3-Only Ligands Allows Complementary Apoptotic Function]</ref> <ref> [http://www.cell.com/cancer-cell/fulltext/S1535-6108(02)00127-7 Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics] </ref> | Therefore, the neutralization of Bcl-2 is required for eficient cell-death. BH3 proteins Bad, Bim and Puma bind Bcl-2 and disable its anti-apoptotic activity. BH3 peptides occupy the hydrophobic pocket of Bcl-2 and the sequestered pro-apoptotic proteins are released. This hydrophobic pocket is formed by F97 and Y101. <ref>[http://www.cell.com/molecular-cell/fulltext/S1097-2765(05)01040-3 Differential Targeting of Prosurvival Bcl-2 Proteins by Their BH3-Only Ligands Allows Complementary Apoptotic Function]</ref> <ref> [http://www.cell.com/cancer-cell/fulltext/S1535-6108(02)00127-7 Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics] </ref> | ||
Bcl-2 localized on external mitochondrial membrane can also inhibit the release of cytochrome c from mitochondria. <ref>[http://science.sciencemag.org/content/275/5303/1132.full The Release of Cytochrome c from Mitochondria: A Primary Site for Bcl-2 Regulation of Apoptosis] </ref> <ref>[http://science.sciencemag.org/content/275/5303/1129.full Prevention of Apoptosis by Bcl-2: Release of Cytochrome c from Mitochondria Blocked] </ref> | Bcl-2 localized on external mitochondrial membrane can also inhibit the release of cytochrome c from mitochondria. <ref>[http://science.sciencemag.org/content/275/5303/1132.full The Release of Cytochrome c from Mitochondria: A Primary Site for Bcl-2 Regulation of Apoptosis] </ref> <ref>[http://science.sciencemag.org/content/275/5303/1129.full Prevention of Apoptosis by Bcl-2: Release of Cytochrome c from Mitochondria Blocked] </ref> | ||
