Bcl-2 Protein Family

The Bcl-2 protein family consists of proteins that contain at least one evolutionarily conserved BH domain out of the four that exist (BH1, BH2, BH3, BH4).  Within this family, there exists pro-apoptotic proteins and anti-apoptotic proteins that interact to govern the fate of the cell. Anti-apoptotic proteins conserve all four BH domains, and include Bcl-2, Bcl-XL, Bcl-W, Mcl-1, and A1. Pro-apoptotic proteins can be subdivided into two groups, those with multiple BH domains such as Bax and Bak, and those with only the BH3 domain such as Bid, Bim, Bad, PUMA, and NOXA (Carter, 2016).

When the cell is not undergoing apoptosis, anti-apoptotic proteins such as Bcl-2 and Bcl-XL sequester Bax and Bak.  When the cell wishes to undergo apoptosis, the anti-apoptotic proteins are sequestered by the BH3-only pro-apoptotic proteins, releasing Bax and Bak, which allow the release of cytochrome C from the mitochondrial membrane, uncoupling the electron transport chain and inducing the activity of caspases. In healthy cells, p53 is a transcription factor for the pro-apoptotic BH3-only proteins Bik, Bid, PUMA, NOXA, as well as for Bax, the pro-apoptotic protein with BH1, BH2, and BH3 homology and the most downstream member of the Bcl-2 family in the regulation of apoptosis (Fridman, 2003). In high grade serous ovarian carcinoma, anti-apoptotic proteins including Bcl-2 and Bcl-xL are overactive and therefore responsible for keeping cancerous cells alive too long (Yokohama, 2017). Different studies have shown a negative correlation between Bcl-xL levels and drug sensitivity in regards to chemotherapy.