The BH3 interacting-domain death agonist, or BID,

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

is a pro-

apoptotic Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes ( morphology) and death. These changes inc ...

member of the 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-

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

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

, Bax, leading to the insertion of Bax into

organelle In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' t ...

membranes, primarily the outer mitochondrial membrane. Bax is believed to interact with, and induce the opening of the mitochondrial voltage-dependent anion channel,

VDAC Voltage-dependent anion channels, or mitochondrial porins, are a class of porin ion channel located on the outer mitochondrial membrane. There is debate as to whether or not this channel is expressed in the cell surface membrane. This major pr ...

. Alternatively, growing evidence suggest that activated Bax and/or

Bak Bak or BAK may refer to: Computer * Bak file * ''Betrayal at Krondor'', a DOS-based role-playing video game * Bill and keep reciprocal payment in telecommunications systems Acronyms * Bcl-2 homologous antagonist killer, a protein involved in pro ...

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 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 A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or re ...

p53, and BID has been shown to be involved in p53-mediated apoptosis. The p53 protein is a

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...

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 Bcl-2 (B-cell lymphoma 2), encoded in humans by the ''BCL2'' gene, is the founding member of the Bcl-2 family of regulator proteins that regulate cell death ( apoptosis), by either inhibiting (anti-apoptotic) or inducing (pro-apoptotic) apoptosi ...

, * CASP2, * CASP8, * MCL1, and * RPA.

Cleavage

Several reports have demonstrated that

caspase Caspases (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases) are a family of protease enzymes playing essential roles in programmed cell death. They are named caspases due to their specific cyst ...

-8, and its substrate BID, are frequently activated in response to certain

stimuli in a death receptor-independent manner. N-hydroxy-L-arginine (NOHA), a stable intermediate product formed during the conversion of L-arginine to

nitric oxide Nitric oxide (nitrogen oxide or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its ...

activates caspase-8. Activation of caspase-8, and subsequent BID cleavage participate in cytochrome-c mediated apoptosis. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mediated activation of caspase-9 via cytochrome-c release has been shown to result in the activation of caspase-8 and Bid cleavage. Aspirin and Curcumin (diferuloylmethane) too activate caspase-8 to cleave and translocate Bid, induced a conformational change in and translocation of Bax and cytochrome-c release.

References

External links

* {{DEFAULTSORT:Bh3 Interacting-Domain Death Agonist Apoptosis Programmed cell death Proteins

Interactions

Cleavage

See also

References

External links