Bcl-2 homologous antagonist killer

From WikiMD's Wellness Encyclopedia

Bcl-2 Homologous Antagonist/Killer (BAK) is a pro-apoptotic member of the Bcl-2 protein family, which plays a significant role in the regulation of apoptosis. BAK, along with its counterparts such as Bcl-2 and Bax, is crucial in the intrinsic pathway of apoptosis, mediating mitochondrial outer membrane permeabilization (MOMP), which is a pivotal step in the apoptotic process.

Structure[edit | edit source]

BAK is a multi-domain protein that includes BH1, BH2, BH3, and a transmembrane domain. The BH3 domain is essential for its pro-apoptotic activity, as it enables BAK to interact with other members of the Bcl-2 family. The structure of BAK allows it to oligomerize on the mitochondrial membrane, forming pores that lead to the release of cytochrome c and other pro-apoptotic factors from the mitochondria into the cytosol.

Function[edit | edit source]

The primary function of BAK is to promote apoptosis by disrupting the mitochondrial membrane potential and facilitating the release of cytochrome c, a critical step in the activation of caspases that execute cell death. BAK is kept in check by anti-apoptotic proteins such as Bcl-2 and Bcl-xL, which bind to BAK and inhibit its pro-apoptotic activity. Upon receiving a death signal, BAK is activated, often through the displacement of these inhibitory interactions by BH3-only proteins, leading to its oligomerization and the initiation of the apoptotic process.

Regulation[edit | edit source]

The activity of BAK is tightly regulated by various mechanisms, including transcriptional regulation, post-translational modifications, and interactions with other Bcl-2 family members. Phosphorylation and ubiquitination are among the post-translational modifications that can influence BAK's pro-apoptotic activity. Additionally, the balance between pro-apoptotic and anti-apoptotic Bcl-2 family proteins is crucial for the regulation of BAK and the decision between cell survival and death.

Clinical Significance[edit | edit source]

Alterations in BAK expression or function have been implicated in the development and progression of several diseases, including cancer. Overexpression of anti-apoptotic Bcl-2 family proteins, leading to the inhibition of BAK, is a common feature in many types of cancer, contributing to resistance to apoptosis and the survival of malignant cells. Consequently, targeting the Bcl-2 family proteins to modulate BAK activity has emerged as a therapeutic strategy in cancer treatment.

Research and Therapeutic Approaches[edit | edit source]

Research into BAK and its role in apoptosis has led to the development of drugs designed to mimic BH3-only proteins, known as BH3 mimetics. These drugs aim to displace BAK from its inhibitors, thereby promoting apoptosis in cancer cells. One example of such a drug is Venetoclax, which targets Bcl-2 and has shown promise in the treatment of certain types of leukemia.

See Also[edit | edit source]

References[edit | edit source]


Contributors: Prab R. Tumpati, MD