Apoptosis is closely regulated by the BCL-2 family of proteins, along with other biochemical pathways¹

BCL-2 plays a pivotal role in the intrinsic initiation of apoptosis^1-3

BCL-2 is part of a larger family of structurally and functionally related proteins collectively known as the BCL-2 family. BCL-2 family proteins, which act primarily at the mitochondrial level, consist of 2 main groups^1-3:

• Pro-survival (anti-apoptotic) proteins, such as BCL-2 itself, which inhibit apoptosis by sequestering pro-death proteins²
• Pro-death (pro-apoptotic) proteins, such as BAK and BAX, which promote apoptosis through the release of cytochrome c^1,2

In normal cells, apoptosis initiation relies on a balance between these 2 types of proteins within the BCL-2 family.²

• Pro-death proteins become unbound from pro-survival proteins in response to cellular stress^1,2,4
• The release of pro-death proteins initiates a signalling cascade that ultimately results in apoptosis^1,2,4

BAK=BCL-2-antagonist/killer 1; BAX=BCL-2 associated X protein; BCL-2=B-cell lymphoma 2.

References: 1. Adams JM, Cory S. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene. 2007;26(9):1324-1337. 2. Plati J, Bucur O, Khosravi-Far R. Apoptotic cell signaling in cancer progression and therapy. Integr Biol (Camb). 2011;3(4):279-296. 3. Czabotar PE, Lessene G, Strasser A, Adams JM. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol. 2014;15(1):49-63. 4. Fulda S, Gorman AM, Hori O, Samali A. Cellular stress responses: cell survival and cell death. Int J Cell Biol. 2010;2010:214074.