Cancer therapeutics based on BCL-2 functional conversion
- 331 Downloads
The BCL-2 protein family plays a key role in the regulation of ‘intrinsic’ apoptosis by regulating the integrity of the mitochondrial outer membrane (MOM). The BCL-2 family of proteins consists of both anti-apoptotic and pro-apoptotic members. These proteins possess one to four BCL-2 Homology (BH) domains and fall into three functional groups. The anti-apoptotic proteins include BCL-2, BCL-XLand MCL-1, which possess BH1-4 domains. The pro-apoptotic BCL-2 family members are divided into two subclasses, comprising the BH3 only proteins such as NOXA and PUMA and multi-domain proteins such as BAK and BAX which possess the BH1-3 domains. The balance between the expression of pro- and anti- death BCL-2 proteins determines the cell fate as pro-survival BCL-2 members bind and inhibit the activity of pro-death members. The BH3-only proteins are upregulated upon cellular stress such as DNA damage or oncogene activation and then bind pro-survival proteins, preventing their inhibition of BAX and...
- 5.Pearce MC, Gamble JT, Kopparapu PR, O’Donnell EF, Mueller MJ, Jang HS, Greenwood JA, Satterthwait AC, Tanguay RL, Zhang X-K, Kolluri SK (2018) Induction of apoptosis and suppression of tumor growth by Nur77-derived Bcl-2 converting peptide in chemoresistant lung cancer cells. Oncotarget 9:26072–26085CrossRefGoogle Scholar