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.

BH3 interacting domain death agonist has been shown to interact with is_associated_with::Bcl-2, is_associated_with::MCL1, is_associated_with::Caspase 8  and is_associated_with::Caspase 2.

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.