Table 2. Classification, role, and interaction of Bcl-2 family proteins in cancer.
| Bcl-2 family protein (Sub-family)a | Activityb | Role in cancerc | Bcl-2 family interacting proteinsd | References |
|---|---|---|---|---|
| Bax (Multidomain) | Pro-apoptotic effector | Targets the endoplasmic reticulum, and the mitochondria. When activated, it promotes mitochondrial fusion in non-cancerous cells and fission in apoptotic cells. | Mcl-1, Bfl-1, Bcl-XL, Bcl-2, Bcl-w, Bcl-B, Puma, Bim, and tBid | [47, 55, 56] |
| Bak (Multidomain) | Pro-apoptotic effector | Binds to the mitochondrial outer membrane (MOM) and endoplasmic reticulum membrane (ERM). It promotes mitochondrial fusion in normal cells and fission in apoptotic cells. | Mcl-1, Bfl-1, Bcl-XL, Puma, Bim, and tBid | [47, 55, 57] |
| Bok (Multidomain) | Pro-apoptotic effector | Targets MOM and promotes MOMP. Its induction in apoptosis is independent of BH3-only activation. | Mcl-1 and Bfl-1 | [55–58] |
| Bid (BH3-Only) | Pro-apoptotic initiator | Upon its activation by caspase 8, tBid gets confined within the location of MOM. It promotes apoptosis via the activation of apoptotic proteins (Bax/Bak) to permeabilize MOM. | Mcl-1, Bfl-1, Bcl-XL, Bcl-2, Bcl-w, Bcl-B, Bax, and Bak | [51, 55, 56] |
| Bim (BH3-Only | Pro-apoptotic initiator | Inhibits anti-apoptotic proteins. It directly binds and activates multidomain pro-apoptotic effectors. | Mcl-1, Bfl-1, Bcl-XL, Bcl-2, Bcl-w, Bcl-B, Bax, and Bak | [55, 59] |
| Bad (BH3-Only) | Pro-apoptotic initiator | Inhibits anti-apoptotic proteins which allow the activation of multidomain pro-apoptotic effectors. | Bcl-2, Bcl-XL and, Bcl-w | [55, 59] |
| Noxa (BH3-Only) | Pro-apoptotic initiator | Inhibits anti-apoptotic proteins which allow the activation of multidomain pro-apoptotic effectors. | Mcl-1, and Bfl-1 | [55, 59] |
| Puma (BH3-Only) | Pro-apoptotic initiator | Inhibits anti-apoptotic proteins. It directly binds and activates multidomain pro-apoptotic effectors. | Mcl-1, Bfl-1, Bcl-XL, Bcl-2, Bcl-w, Bax, and Bak | [55, 59] |
| Bcl-B | Anti-apoptotic factor | Selectively inhibits Bax pro-apoptotic effector and BH3-only pro-apoptotic initiators. | Bax, Bim and, tBid | [55, 57, 59] |
| Bcl-w | Anti-apoptotic factor | Inhibits Bax pro-apoptotic effector and BH3-only pro-apoptotic initiators. | Bax, Bad, Bim, tBid and, puma | [55, 57, 59] |
| Bcl-2 | Anti-apoptotic factor | Inhibits both pro-apoptotic effectors and BH3-only pro-apoptotic initiators. | Bax, Bad, Bim, tBid and, Puma | [55, 57, 59] |
| Bcl-XL | Anti-apoptotic factor | Inhibits both pro-apoptotic effectors and BH3-only pro-apoptotic initiators. | Bax, Bak, Bad, Bim, tBid and, puma | [55, 57, 59] |
| Bfl-1 | Anti-apoptotic factor | Inhibits both pro-apoptotic effectors and BH3-only pro-apoptotic initiators. | Bax, Bak, Bok, Bim, tBid, Noxa and, puma | [55, 57, 59] |
| Mcl-1 | Anti-apoptotic factor | Inhibits both pro-apoptotic effectors and BH3-only pro-apoptotic initiators. | Bax, Bak, Bim, tBid, Noxa and, Puma | [55, 57, 59] |
amember of the Bcl-2 family of proteins expressed in various types of cancer. bapoptotic activities of members of proteins belonging to the Bcl-2 family of proteins. croles of various members of the Bcl-2 family of proteins in cancer. dinteractions of different members of the Bcl-2 family of proteins in cancer.