Bcl-2-associated death promoter
Bcl-2-associated death promoter (BAD) is a pro-apoptotic member of the Bcl-2 family of proteins. It plays a crucial role in the regulation of apoptosis, a form of programmed cell death, by promoting cell death in response to various cellular stress signals.
Structure[edit | edit source]
BAD is a member of the Bcl-2 family, which is characterized by the presence of one or more Bcl-2 homology domains (BH domains). BAD contains the BH3 domain, which is essential for its pro-apoptotic activity. The BH3 domain allows BAD to interact with and neutralize anti-apoptotic proteins such as Bcl-2 and Bcl-xL, thereby promoting apoptosis.
Function[edit | edit source]
BAD promotes apoptosis by binding to and inhibiting the function of anti-apoptotic Bcl-2 family members. This interaction releases pro-apoptotic factors such as Bax and Bak, which then oligomerize and form pores in the mitochondrial outer membrane. This leads to the release of cytochrome c and other pro-apoptotic factors from the mitochondria into the cytosol, triggering the activation of caspases and the execution of apoptosis.
Regulation[edit | edit source]
The activity of BAD is regulated by phosphorylation. When BAD is phosphorylated by kinases such as Akt or Protein kinase A, it is sequestered in the cytosol by binding to 14-3-3 proteins, which prevents it from interacting with Bcl-2 and Bcl-xL. Dephosphorylation of BAD, on the other hand, allows it to translocate to the mitochondria and promote apoptosis.
Clinical Significance[edit | edit source]
Dysregulation of BAD and other Bcl-2 family members is implicated in various diseases, including cancer, neurodegenerative diseases, and autoimmune disorders. Overexpression of anti-apoptotic Bcl-2 family proteins can lead to resistance to apoptosis, contributing to the survival and proliferation of cancer cells. Conversely, enhancing the pro-apoptotic activity of BAD is being explored as a potential therapeutic strategy for inducing cell death in cancer cells.
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Contributors: Prab R. Tumpati, MD
