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Bcl-2 homologous antagonist/killer (BAK) is a pro-apoptotic protein that plays a crucial role in the regulation of apoptosis, or programmed cell death. This protein is encoded by the BAK1 gene in humans and is a member of the BCL-2 protein family. The BCL-2 family consists of both pro-apoptotic and anti-apoptotic proteins that regulate cell death and survival, maintaining cellular homeostasis.
BAK contains four Bcl-2 homology (BH) domains: BH1, BH2, BH3, and BH4. These domains are composed of nine α-helices, with a hydrophobic α-helix core surrounded by amphipathic helices and a transmembrane C-terminal α-helix anchored to the mitochondrial outer membrane (MOM). The BH3 domain is particularly important for its pro-apoptotic activity, as it interacts with other BCL-2 family members to promote apoptosis .
BAK functions as a pro-apoptotic regulator involved in a wide variety of cellular activities. In healthy mammalian cells, BAK localizes primarily to the MOM but remains in an inactive form until stimulated by apoptotic signaling. Upon activation, BAK undergoes a conformational change, leading to the formation of oligomers that permeabilize the MOM. This permeabilization results in the release of cytochrome c and other pro-apoptotic factors from the mitochondria, ultimately leading to cell death .
BAK interacts with several other proteins to regulate its activity. In its inactive form, BAK is maintained by interactions with VDAC2, Mtx2, and other anti-apoptotic members of the BCL-2 protein family. Upon activation, BAK interacts with the tumor suppressor protein P53, which further promotes its pro-apoptotic activity .
The pro-apoptotic function of BAK is crucial for maintaining cellular homeostasis, but dysregulation of BAK can contribute to various diseases. Overexpression of BAK has been linked to neurodegenerative and autoimmune diseases, while inhibition of BAK is associated with certain cancers. For instance, dysregulation of the BAK gene has been implicated in human gastrointestinal cancers, indicating that the gene plays a part in the pathogenesis of some cancers .
Mouse anti-human BAK antibodies are commonly used in research to study the function and regulation of BAK in human cells. These antibodies are generated by immunizing mice with human BAK protein, leading to the production of antibodies that specifically recognize and bind to human BAK. These antibodies are valuable tools for investigating the role of BAK in apoptosis and its involvement in various diseases.