BH3 interacting-domain death agonist

The BH3 interacting-domain death agonist, or BID, is_associated_with::gene is a pro-apoptotic member of the is_associated_with::Bcl-2 protein family. Bcl-2 family members share one or more of the four characteristic domains of homology entitled the Bcl-2 homology (BH) domains (named BH1, BH2, BH3 and BH4), and can form hetero- or homodimers. Bcl-2 proteins act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities.

Interactions
BID is a pro-apoptotic Bcl-2 protein containing only the BH3 domain. In response to apoptotic signaling, BID interacts with another Bcl-2 family is_associated_with::protein, Bax, leading to the insertion of Bax into is_associated_with::organelle membranes, primarily the outer is_associated_with::mitochondrial membrane. Bax is believed to interact with, and induce the opening of the mitochondrial voltage-dependent anion channel, VDAC. Alternatively, growing evidence suggest that activated Bax and/or Bak form an oligomeric pore, MAC in the outer membrane. This results in the release of cytochrome c and other pro-apoptotic factors (such as SMAC/DIABLO) from the mitochondria, often referred to as mitochondrial outer membrane permeabilization, leading to activation of is_associated_with::caspases. This defines BID as a direct activator of Bax, a role common to some of the pro-apoptotic Bcl-2 proteins containing only the BH3 domain.

The anti-apoptotic Bcl-2 proteins, including Bcl-2 itself, can bind BID and inhibit BID's ability to activate Bax. As a result, the anti-apoptotic Bcl-2 proteins may inhibit apoptosis by sequestering BID, leading to reduced Bax activation.

The expression of BID is upregulated by the tumor suppressor is_associated_with::p53, and BID has been shown to be involved in p53-mediated apoptosis. The p53 protein is a is_associated_with::transcription factor that, when activated as part of the cell's response to stress, regulates many downstream target genes, including BID. However, p53 also has a transcription-independent role in apoptosis. In particular, p53 interacts with Bax, promoting Bax activation and the insertion of Bax into the mitochondrial membrane.

The BH3 interacting-domain death agonist has been shown to interact with:
 * ATR/ATRIP,
 * BCL2,
 * CASP2,
 * CASP8,
 * is_associated_with::MCL1, and
 * RPA.

Cleavage


Several reports have demonstrated that is_associated_with::caspase-8, and its substrate BID, are frequently activated in response to certain is_associated_with::apoptotic stimuli in a death receptor-independent manner. N-hydroxy-L-arginine (NOHA), a stable intermediate product formed during the conversion of L-arginine to is_associated_with::nitric oxide activates caspase-8. Activation of caspase-8, and subsequent BID cleavage participate in is_associated_with::cytochrome-c mediated is_associated_with::apoptosis. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mediated activation of caspase-9 via is_associated_with::cytochrome-c release has been shown to result in the activation of caspase-8 and Bid cleavage. is_associated_with::Aspirin and is_associated_with::Curcumin (diferuloylmethane) too activate caspase-8 to cleave and translocated Bid, induced a conformational change in and translocation of Bax and is_associated_with::cytochrome-c release.