BID Human

The BH3 Interacting Domain Death Agonist (BID) is a pro-apoptotic member of the Bcl-2 protein family. This family of proteins plays a crucial role in the regulation of apoptosis, a form of programmed cell death essential for maintaining cellular homeostasis and development. BID is unique among the Bcl-2 family members as it contains only the BH3 domain, which is critical for its interaction with other Bcl-2 family proteins and its pro-apoptotic activity .

The BID gene is located on chromosome 22 in humans and encodes a protein that is found in both cytosolic and membrane locations . The protein lacks a C-terminal signal-anchor segment, which distinguishes it from other Bcl-2 family members . The BH3 domain within BID is essential for its ability to heterodimerize with either pro-apoptotic proteins like Bax or anti-apoptotic proteins like Bcl-2 .

BID plays a pivotal role in the intrinsic pathway of apoptosis. Upon activation by caspase-8 in response to death receptor signaling (such as Fas/TNF-R1), BID is cleaved into its truncated form, tBid . This truncated form translocates to the mitochondria, where it facilitates the release of cytochrome c and other pro-apoptotic factors, leading to the activation of downstream caspases and the execution of apoptosis .

BID interacts with several key proteins in the apoptosis pathway. It directly activates Bax, a pro-apoptotic Bcl-2 family member, leading to the insertion of Bax into the outer mitochondrial membrane . This interaction results in mitochondrial outer membrane permeabilization (MOMP) and the release of apoptogenic factors . Anti-apoptotic Bcl-2 proteins can bind to BID and inhibit its ability to activate Bax, thereby preventing apoptosis .

The expression of BID is regulated by the tumor suppressor protein p53, which is involved in the cellular response to DNA damage and stress . BID has been implicated in p53-mediated apoptosis, highlighting its role in tumor suppression . Additionally, BID’s involvement in apoptosis makes it a potential target for therapeutic intervention in diseases where apoptosis is dysregulated, such as cancer and neurodegenerative disorders .

Recombinant human BID protein is produced using various expression systems, including baculovirus-insect cells . This recombinant protein is used in research to study the mechanisms of apoptosis and to develop potential therapeutic strategies targeting the apoptotic pathway .